Mayo Clinic Researchers find Adding Epratuzumab to Standard Therapy for Aggressive Lymphoma Produces Significant Overall Response

Please see article at the following link on mayoclinic.org.  http://www.mayoclinic.org/news2008-rst/4802.html

MM Updates 6-19-08

Ask the Doctor

Stem Cells for Transplant: How Much is Enough?
“My doctor has tried to collect stem cells for my autologous transplant, but
so far he has not collected enough CD34+ cells. What are CD34+ cells? How
much is enough?”

Philip McCarthy MD, Roswell Park Cancer Institute, New York responds:

CD34+ cells are a type of white blood cell that has a particular marker on
its cell surface. CD34+ cells contain the stem cells of the blood cell
system. These stem cells can produce exact copies of themselves to maintain
a constant supply in the bone marrow. They also produce other cells, which
eventually evolve into white blood cells, red blood cells and platelets.

If the number of CD34+ cells infused into a patient following high-dose
chemotherapy or radiotherapy is too small, the patient may not be able to
produce a sufficient number of blood cells after transplant. The number of
stem cells required for transplant differs depending on the stem cell source
(blood versus bone marrow versus cord blood).

When harvesting stem cells for an autologous blood stem cell transplant,
usually a minimum of two million CD34+ cells per kilogram of patient body
weight are required. There is some data suggesting that a patient engrafts
better with more CD34+ cells, but this is not uniformly accepted by all BMT
centers. Twice that amount may be collected, particularly if the patient is
considering more than one transplant.

Before stem cells can be collected from the bloodstream, they must first be
“mobilized” or moved there from the bone marrow.  A cell growth factor
called Neupogen(r) (filgrastim, G-CSF), given by injection to patients
several days before the stem cell collection, usually moves enough stem
cells from the bone marrow to the bloodstream. Unfortunately, in some
patients, particularly those who have had a lot of prior chemotherapy,
Neupogen(r) alone does not work. When this occurs, Neupogen(r) or another
cell growth factor called Leukine(r) (sargramostim, GM-CSF), plus
chemotherapy may be used to mobilize enough stem cells for collection.
Another option is to supplement the cells collected from the bloodstream
with a bone marrow harvest.

Patients with multiple myeloma are usually able to produce sufficient stem
cells for collection with Neupogen(r) alone. Patients with Hodgkin’s disease
or non-Hodgkin’s lymphoma can have more difficulty.  Approximately 25-30%
don’t mobilize properly with Neupogen(r) alone.

A new drug called plerixafor (Mozobil(tm)), when used with Neupogen(r),
appears to increase the number of stem cells that can be moved into the
bloodstream for collection. This drug has not yet been approved by the FDA.
In two Phase III clinical trials involving 600 patients with multiple
myeloma or non-Hodgkin’s lymphoma, those who received a combination of
Mozobil(tm) and Neupogen(r) were able to collect the targeted number of
cells for transplant faster than those who received Neupogen(r) alone. In
the trial involving patients with multiple myeloma, 72% of those who
received the combination of Mozobil(tm) and Neupogen(r) produced the target
number of stem cells within two days or less. In contrast, only 34% of those
who received Neupogen(r) alone reached the target after two days of stem
cell collection. In the trial involving patients with non-Hodgkin’s
lymphoma, 59% of those who received Mozobil(tm) and Neupogen(r) achieved the
target number of stem cells in four days or less. Only 20% of patients who
received Neupogen alone reached the target in four days.

For related and unrelated donor blood stem cell transplants, most people
will mobilize well with Neupogen(r) alone. However, 3-5 percent of normal
donors don’t mobilize. When this occurs, the stem cells collected from the
bloodstream is supplemented by a bone marrow harvest, rather than by the
addition of chemotherapy.

Although it is possible to transplant a patient with less than the optimal
amount of CD34+ stem cells, it is dicey. It will take longer for the patient
to begin producing sufficient blood cells, during which time he or she will
be at risk for infection and bleeding. Some patients could have long-term
issues with poor count recovery, such as prolonged red cell and platelet
transfusion requirements or chronic Neupogen(r) or Leukine(r) usage.
Sometimes the low red counts do not respond to red cell stimulation with
erythropoietin, forcing the need for prolonged red cell transfusions that
could lead to iron overload. If the patient ever needs any type of
chemotherapy or radiation following transplant, poor marrow function might
make this therapy impossible.

There is a cooperative group study examining the long-term use of
lenalidomide or placebo after transplant to prevent recurrence following
autotransplant for myeloma. Lenalidomide can suppress the white blood cell
and platelet counts. Poor marrow function could prevent this drug from being
used for maintenance therapy. A high CD34+ count does not guarantee fast
count recovery but it helps ensure a better outcome.

Clinical Trial for GVHD Sores
Blood and Marrow Transplant Information Network (BMT InfoNet) | 2310 Skokie
Valley Rd | Suite 104 | Highland Park | IL | 60035

Vol. 17, No.3 | March 2007
(c)Copyright 2007 BMT InfoNet
BMT InfoNet
2310 Skokie Valley Road, Suite 104, Highland Park, IL 60035
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
New Study: Life After Transplant
Researchers at Mt. Sinai Medical Center are recruiting transplant survivors
for a study about an intervention that may help people manage physical and
emotional symptoms after transplant. You may be eligible to participate in
this study if you:

* are nine months or more post-transplant
* are at least 18 years of age
* peak English
Participants will complete a 45-minute telephone interview that includes
questions about their background, how they feel emotionally and physically,
their personality, and their relationships with others. They will also be
asked to complete a questionnaire packet.

They will be assigned to one of four writing groups. Each group will write
about a different topic once a week for four weeks.

For more information, contact Christine Rini (Principal Investigator) at
212-659-5555 or Lisa Wu (Project Coordinator) at 212-659-5586. You can also
email christine.rini@mssm. edu or lisa.wu@mssm.edu.

Living Now: A Survivor’s Conference on Life after Transplant
Blood and Marrow Transplant Information Network (BMT InfoNet) | 2310 Skokie
Valley Rd | Suite 104 | Highland Park | IL | 60035

Vol. 17, No.3 | March 2007
(c)Copyright 2007 BMT InfoNet
BMT InfoNet
2310 Skokie Valley Road, Suite 104, Highland Park, IL 60035
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
Amgen: Denosumab Improves Bone Vs Fosamax

Reuters Health – May. 20, 2008
LOS ANGELES (Reuters) – Amgen Inc said on Monday a trial of its experimental
osteoporosis drug, denosumab, showed it increased bone density at the hip in
post- menopausal women who switched from Merck & Co Inc’s Fosamax.
The news sent the biotechnology company’s shares up 2 percent.
The one-year study of 504 patients with low bone mineral density (BMD)
showed the relative magnitude of improvement at the total hip was about 80
percent greater in patients injected twice a year with denosumab, compared
with the group that continued with weekly oral doses of Fosamax, also known
as alendronate.
Amgen did not disclose specific results for the trial’s other goals, but
said patients treated with denosumab achieved significantly greater bone
density gains at all sites measured.
The company said the incidence and types of side effects, including
cancerous tumors and infection, were balanced between the two treatment
groups.
“This is important, as many (Wall) Street observers have worried about
infection risk,” Bear Stearns analyst Mark Schoenebaum said in a research
note.
Amgen said the most common side effects seen in the trial included back pain
and joint pain.
“This is the second phase 3, head-to-head study demonstrating that
administration of denosumab resulted in superior BMD gains versus those
achieved with alendronate,” Roger Perlmutter, Amgen’s executive vice
president of research and development, said in a statement.
The biotechnology company expects results from its 8,000- patient phase 3
study evaluating denosumab’s impact on fracture risk in women with
post-menopausal osteoporosis in the second half of this year.
Amgen is developing denosumab-a bioengineered antibody that targets a
protein involved with the activity of bone- destroying cells called
osteoclasts-as a treatment for osteoporosis patients, as well as for cancer
patients whose disease has spread to the bone.
Amgen shares, which closed at $42.34 on Nasdaq, were up 2 percent at $43.26
in after hours trading.
(Reporting by Deena Beasley; editing by Carol Bishopric, Leslie Gevirtz)
Copyright (c) 2006 Reuters Limited. All rights reserved. Republication or
redistribution of Reuters content, including by framing or similar means, is
expressly prohibited without the prior written consent of Reuters. Reuters
shall not be liable for any errors or delays in the content, or for any
actions taken in reliance thereon. Reuters and the Reuters sphere logo are
registered trademarks and trademarks of the Reuters group of companies
around the world.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Cancer News
Current And Emerging Drugs Have Not Yet Shown An Advantage In Survival Over
Velcade In The Treatment Of Relapsed Multiple Myeloma
NewsRx.com
May 15, 2008

Decision Resources, one of the world’s leading research and advisory firms
focusing on pharmaceutical and healthcare issues, finds that a drug’s effect
on overall survival is the attribute that most influences surveyed
hematologists’ prescribing decisions in relapsed multiple myeloma treatment.
Clinical data and expert opinion show that current and emerging therapies
have not yet demonstrated an advantage in this attribute over the market
sales-leader, Millennium Pharmaceuticals/Johnson & Johnson’s Velcade.
The new report entitled Multiple Myeloma: Physicians Seek an Agent with
Improved Overall Survival for Patients with Relapsed Disease finds that an
emerging agent administered in combination with Velcade that improves median
overall survival compared to treatment with Velcade alone would earn a 45
percent patient share in multiple myeloma, according to surveyed
hematologists. Although Velcade is the multiple myeloma market sales-leader,
the clinical gold standard treatment for relapsed disease is
lenalidomide/dexamethasone (Celgene’s Revlimid, Merck’s Decadron, generics)
owing to its superiority in both efficacy and delivery.
“While overall survival is considered to be the most important indicator of
efficacy by physicians who treat oncology patients,
lenalidomide/dexamethasone has clearly demonstrated an improvement in other
efficacy parameters and therefore earns clinical gold-standard status,” said
Clair Gricks, Ph.D., analyst at Decision Resources.
Copyright 2008, Blood Weekly via NewsRx.com
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Cancer News
Data Finds REVLIMID As A Monotherapy Is Effective And Well-tolerated For
Previously Treated Multiple Myeloma Patients
NewsRx.com
June 12, 2008

The Moffitt Cancer Center said findings from a clinical trial presented at
the American Society of Clinical Oncology (ASCO) meeting evaluating REVLIMID
(lenalidomide) as a monotherapy is both effective and well-tolerated in
patients who have been previously treated for multiple myeloma with two or
more therapies.
In the study, 26% of relapsed refractory multiple myeloma patients treated
with REVLIMID as a single achieved an overall response, either complete or
partial remission, and 66% of patients experienced stable disease. The
median overall survival was 1.9 years with 41% of patients alive after three
years. Prior to this innovative therapy the median overall survival was less
than a year. Additionally, the duration of response was 13 months.
“REVLIMID is a novel, oral, targeted immune modulator cancer therapy with
impressive clinical data in both newly diagnosed and previously treated
multiple myeloma that shows REVLIMID can provide durable, long-lasting
results for patients,” said Dr. Mohamad Hussein, Head Multiple Myeloma
Section, Moffitt Cancer Center. “This study demonstrates that REVLIMID is
effective in treating patients in which other therapies have failed without
complimentary steroids or chemotherapy that can potentially cause serious
side effects helping patients to live longer with a better quality of life.”

Multiple myeloma is a cancer of one of the immune cells that affects
production of red cells, white cells and platelets. It is the second most
prevalent and fastest growing of the blood cancers, affecting an estimated
750,000 people worldwide and 60,000 patients in the U.S.
REVLIMID is the newest of what are called immune modulators which have
changed the outlook for patients with multiple myeloma and enable doctors to
treat the previously incurable cancer as a chronic, manageable condition. It
is an oral drug that can be taken at home and doesn’t have some of the
difficult side effects associated with traditional chemotherapy because it
targets the cancer cells directly along with the factors that support their
growth.
About Moffitt Cancer Center
Located in Tampa, Florida, Moffitt Cancer Center (www.moffitt.org) is the
only Florida-based cancer center with the NCI designation as a Comprehensive
Cancer Center for its excellence in research and contributions to clinical
trials, prevention and cancer control. Moffitt currently has 15 affiliates
in Florida, one in Georgia and two in Puerto Rico. Additionally, Moffitt is
a member of the National Comprehensive Cancer Network, a prestigious
alliance of the country’s leading cancer centers, and is listed in U.S. News
& World Report as one of “America’s Best Hospitals” for cancer and ear, nose
and throat. Moffitt’s sole mission is to contribute to the prevention and
cure of cancer.
Copyright 2008, Health Risk Factor Week via NewsRx.com
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

A Guide to Food Additives

Cancer News

Chemical Cuisine: A Guide To Food Additives

Nutrition Action Health Letter

May 6, 2008

Is calcium stearoyl lactylate safe? Which food coloring is made from the bodies of dried, pulverized insects? Is aspartame the safest artificial sweetener? Or is it sucralose?

Food additives thicken our salad dressings, prevent our sliced ham from turning gray, make our microwave popcorn smack of butter, and sweeten our diet sodas. They also make dried apple bits taste like peaches and sugar water look like fruit juice.

While most food additives are safe, some haven’t been adequately tested. And a few could be dangerous.

Our Cheminai Cuisine guide tells you which are which.

This alphabetical listing of the most common food additives includes what they’re used for, some of the foods in which they’re found, and our assessment of their safety. (A more detailed list is online at www.cspinet.org/reports/chemcuisine.htm.)

* Acesulfame Potassium.

Artificial sweetener: Chewinggum, diet soda, no-sugar-added baked goods and desserts, tabletop sweetener (Sunett).

Poorly done safety tests in the 1970s suggested that acesulfame potassium may cause cancer. The Food and Drug Administration has refused to require better studies. Acesulfame potassium is often used together with sucralose.

* Alginate, Propylene Glycol Alginate.

Foam stabilizers, thickening agents: Beer, candy, cheese, ice cream, yogurt.

They’re made from seaweed (kelp).

* Alpha Tocopherol (Vitamin E).

Antioxidant, nutrient: Oils.

Small amounts are added to oils to keep them from going rancid and to other foods to pump up the vitamin E.

* Artificial and Natural Flavoring.

Breakfast cereal, candy, soda, many other foods.

Most of the hundreds of chemicals used to mimic natural flavors also occur in nature and are probably safe. But flavorings are often used in junk foods to mask the absence of natural ingredients (fruit, for example). Flavorings may include additives like MSG or HVP, to which some people are sensitive.

* Ascorbic Acid (Vitamin C), Erythorbic Acid.

Antioxidant, color stabilizer, nutrient: Cereal, cured meat, fruit drinks.

It helps maintain the red color of ham, bacon, and other cured foods and it inhibits the formation of cancer-promoting nitrosamines (see Sodium Nitrite). Vitamin C is also used to pump up the vitamin content of foods like “fruit” drinks. Sodium ascorbate is a form of ascorbic acid that dissolves easily. Erythorbic acid is chemically similar to ascorbic acid, but it isn’t a vitamin.

*Aspartame (NutraSweet).

Artificial sweetener: Frozen desserts, diet soda, tabletop sweetener (Equal).

Disturbing new Italian research in animals indicates that longterm consumption may increase the risk of leukemia, lymphoma, and breast cancer. Although some people report dizziness, hallucinations, or headaches after drinking diet soda, only one of the controlled studies that looked for a link found one (to headaches). People with the rare disease PKU (phenylketonuria) need to avoid aspartame.

* Beta-Carotene.

Coloring, nutrient: Coffee creamer, margarine, butter, candy.

It’s an orange pigment that the body converts to vitamin A.

* Brominated Vegetable oil (BVO).

Clouding agent, emulsifier: Soft drinks.

It’s occasionally used to keep flavor oils in suspension and give a cloudy appearance to citrus-flavored soft drinks. Small residues of BVO remain in body fat, but it’s unclear whether they pose any risk.

* Butylated Hydroxyanisole (BHA).

Antioxidant: Cereal packages, chewing gum, oil, potato chips.

It retards rancidity in fats, oils, and foods that contain oil. According to the federal government’s National Toxicology Program, it is “reasonably anticipated to be a human carcinogen,” based on animal studies.

* Butytated Hydroxytoluene (BHT).

Antioxidant: Cereal, chewing gum, oil, potato chips.

It keeps oils from going rancid. In some animal studies it increased the risk of cancer; in others it decreased the risk.

* Caffeine.

Flavoring, stimulant: Added to soft drinks and water. Occurs naturally in coffee, tea, cocoa, and chocolate.

It improves alertness and endurance, especially for the sleepdeprived, but can also interfere with sound sleep and make you jittery. If you have those symptoms, consider cutting back. Caffeine is mildly addictive; it causes headaches, irritability, or sleepiness when you go too long without it. High doses (more than 200 mg a day) may increase the risk of miscarriage or rare birth defects. Avoid caffeine if you are pregnant or are trying to become pregnant.

* Calcium Propionate, Sodium Propionate.

Preservative: Bread, cake, pie, rolls.

Calcium propionate prevents the growth of mold on bread and rolls. The calcium is a nutrient and the propionate is safe. Since calcium interferes with leavening agents, sodium propionate, which is also safe, is used in pies and cakes.

* Calcium (or Sodium) Stearoyl Lactylate or Sodium Stearoyl Fumarate.

Dough conditioner, whipping agent: Artificial whipped cream, bread dough, cake filling, processed egg whites.

They strengthen bread dough so that it can be used in commercial bread-making machinery. They help produce a more uniform grain and greater bread volume. And they act as whipping agents in dried, liquid, or frozen egg whites and artificial whipped cream.

* Carrageenan.

Stabilizing and thickening agent: Chocolate milk, cottage cheese, icecream, infant formula, jelly.

It comes from seaweed. Large amounts have damaged the colons of test animals, though the small amounts in food are safe.

* Casein, Sodium Caseinate.

Thickening and whitening agent: Coffee creamer, ice cream, ice milk, sherbet.

Casein is the principal protein in milk. Since it’s used in some “non-dairy” and “vegetarian” foods, people who are allergic to milk need to read labels carefully.

* Citric Acid, Sodium Citrate.

Acid, chelating agent, flavoring: Candy, soft drinks, fruit drinks, icecream, instant potatoes, sherbet.

Citric acid is used as a tart flavoring and an antioxidant. Sodium citrate is a buffer that controls the acidity of gelatin desserts, jams, ice creams, candies, and other foods.

Artificial Colorings

They’re used almost exclusively in products with little nutritional value (candy, soda, etc.), so you won’t be missing much if you avoid foods that contain them. The presence of colorings usually signals the absence of fruit or other natural ingredients. Colorings contribute to hyperactivity in some children.

* Blue 1. Baked goods, beverages, candy.

Inadequate tests suggested a small cancer risk.

* Blue 2. Beverages, candy, pet food.

The largest study suggested that it caused brain tumors in male mice. Unfortunately, the Food and Drug Administration concluded that there is “reasonable certainty of no harm.”

* Citrus Red 2. Skin of some Florida oranges.

Studies indicated that it may slightly increase the risk of cancer, but the coloring doesn’t seep through the orange skin into the pulp. Because so little is used, you have only a minuscule increased risk if you eat the peel.

* Green 3. Beverages, candy.

A 1981 industry-sponsored study showed hints of bladder cancer in laboratory animals, but after the FDA reanalyzed the data, it concluded that the dye was safe. Fortunately, Green 3 is rarely used.

* Red 3. Baked goods, candy, cherries in fruit cocktail.

The FDA’s recommendation that Red 3 be bannedbased on evidence that it caused thyroid tumors in rats-was overruled by pressure from the Reagan Administration.

* Red 40. Candy, gelatin dessert, pastries, pet food, sausage, soda.

An FDA review committee acknowledged that the most widely used food dye caused problems in key mouse studies, but said that evidence of harm was not “consistent” or “substantial.”

* Yellow 5. Baked goods, candy, gelatin dessert, per food.

* The second most widely used coloring can cause mild allergic reactions, mostly in the small number of people who suffer allergic reactions to aspirin.

* Yellow 6. Baked goods, beverages, candy, gelatin, sausage.

Industry-sponsored animal tests indicated that the third most widely used dye caused tumors of the adrenal gland and kidney. What’s more, smail amounts of several carcinogens can contaminate Yellow 6. Even so, the FDA concluded that the coloring doesn’t endanger humans. Yellow 6 may also cause allergic reactions.

* Cochineal or Carmine.

Artificial coloring: Beverages, candy, ice cream, yogurt.

Cochineal extract is a red coloring made from the dried and pulverized bodies of insects. Carmine is a more purified coloring made from cochineal. Both have caused rare allergic reactions that range from hives to life-threatening anaphylactic shock.

* Corn Syrup.

Sweetener, thickener: Beverages, cake, candy, cereal, cookies, syrup, yogurt.

Corn syrup-which consists mostly of dextrose-is a sweet, thick liquid made by treating cornstarch with acids or enzymes. It is sometimes dried and used as corn syrup solids in coffee creamers and other dry foods. It has no nutritional value other than calories, it promotes tooth decay, and it is used mainly in foods with little nutritional value.

* Dextrose (Glucose, Corn Sugar).

Sweetener: Bread, cookies, soft drinks.

When added to foods as a sweetener, it means empty calories and tooth decay.

EDTA.

* Chelating agent: Canned shellfish, margarine, mayonnaise, processed fruits and vegetables, salad dressing, sandwich spreads, soft drinks.

Modern food-manufacturing technology leaves trace amounts of metal in food (from metal rollers, blenders, and containers). EDTA (ethylenediamine tetraacetic acid) chelates the metals-that is, it traps impurities that would otherwise make oils rancid and break down artificial colors.

* Ferrous Gluconate.

Coloring, nutrient: Black olives.

It’s used to generate a uniform jet-black color in olives and as a source of iron in foods.

* Fructose.

Sweetener: “Health” foods and drinks.

Pure fructose is used as a sweetener in a small number of foods. Modest amounts are safe and don’t boost blood sugar levels. But large amounts consumed on a regular basis may raise the risk of heart disease by increasing blood triglyceride levels. They may also contribute to obesity because fructose affects hormones that regulate weight and may not curb appetite as much as an equal amount of glucose or sucrose.

* Fumaric Acid.

Tartness agent: Gelatin dessert, pie filling, powdered drinks.

It adds tartness and acidity. To help it dissolve faster in cold water, it’s often mixed with dioctyl sodium sulfosuccinate (DSSX an additive that appears to be safe.

* Gelatin.

Gelling and thickening agent: Beverages, cheese spreads, ice cream, powdered dessert mixes, yogurt.

It’s a protein obtained from animal hides and bones that has less nutritional value than other proteins.

* Glycerin (Glycerol).

Maintains water content: Baked goods, candy, fudge.

It’s a natural component of fat molecules. The body uses it for calories or to make more-complex molecules.

* Gums (Arabic, Furcelleran, Ghatti, Guar, Karaya, Locust Bean, Tragacanth, Xanthan).

Stabilizers, thickening agents: Beverages, candy, cottage cheese, dough, drink mixes, pudding, ice cream, salad dressing.

Gums are derived from natural sources (bushes, trees, seaweed, bacteria). Though poorly tested, they’re probably safe. In rare instances, tragacanth has caused severe allergic reactions.

* High-Fructose Corn Syrup (HFCS).

Sweetener: Soft drinks, many other foods.

This mixture of two sugars (it’s about half fructose, half glucose) has largely replaced table sugar (sucrose) in soft drinks and many other foods because it’s cheaper. Despite the urban myth, it’s not worse for you than sucrose. Like other sugars, it promotes obesity, tooth decay, and-in people with high triglycerides-heart disease.

* Hydrolyzed Vegetable Protein (HVP).

Flavor enhancer: Beef stew, frankfurters, instant soup, sauce mixes.

It consists of plant protein (usually from soybeans) that has been chemically broken down into its amino acid components. HVP brings out the natural flavor of food. It contains MSG, and large amounts may cause reactions in sensitive people (see MSG).

* Inulin.

Fat and sugar substitute, source of fiber: Margarine, baked goods, fillings, dairy foods, frozen desserts, salad dressing.

It’s a naturally occurring soluble fiber. Inulin doesn’t raise blood sugar levels, so it may help people with diabetes. It also stimulates the growth of friendly bacteria in the large intestine.

* Invert Sugar.

Sweetener: Candy, soft drinks.

This 50-50 mixture of two sugars (dextrose and fructose) is sweeter and dissolves better than sucrose (table sugar). It’s nothing but empty calories and it contributes to tooth decay.

* Lactic Acid.

Controls acidity: Carbonated beverages, cheese, frozen desserts, Spanish olives.

It inhibits spoilage in Spanish olives, balances the acidity in cheese, and adds tartness to frozen desserts, carbonated fruitflavored sodas, and other foods.

* Lactose.

Sweetener: Breakfast pastries, whipped topping mixes.

Lactose (milk sugar) is nature’s way of delivering calories to infant mammals. It’s one-sixth as sweet as table sugar and is added to foods as a slightly sweet source of carbohydrates. Some adults have trouble digesting large amounts of lactose.

* Lecithin.

Antioxidant, emulsifier: Baked goods, chocolate, ice cream, margarine.

It occurs naturally in soybean oil and eggs. It keeps oil and water from separating, retards rancidity, reduces spattering, and helps make cakes fluffier.

* Maltitol, Mannitol.

Sweeteners: Candy, chocolate, jam, other sugar-free foods.

Like other sugar alcohols (sorbitol, xylitol), maltitol and mannitol are not well absorbed by the body, so they have fewer calories than table sugar. And they don’t promote tooth decay. Large amounts (above 20 to 30 grams) may have a laxative effect.

* Maltodextrin.

Thickening agent, sweetener: Canned fruit, salad dressing, instant pudding.

It’s made from starch. Some maltodextrins are easily digested and absorbed, while others are chemically processed so that they are “resistant”-they can’t be broken down by digestive enzymes. That makes them an isolated fiber. These resistant maltodextrins may help lower blood sugar levels, but don’t help prevent constipation.

* Mono- and Diglycerides.

Emulsifters: Baked goods, candy, margarine, peanut butter.

They make bread softer, margarine more stable, and caramel less sticky. They also prevent the oil in peanut butter from separating.

* MSG (Monosodium Glutamate).

Flavor enhancer: Chips, frozen entrées, restaurant food, saiad dressing, soup.

MSG is the sodium salt of a common amino acid, glutamic acid. It brings out the flavor of foods. In the 1960s, researchers discovered that large amounts fed to infant mice destroyed brain cells. Careful studies have shown that a small number of people are sensitive to large doses of MSG. Reactions include headache, nausea, weakness, and burning sensations in the back of the neck and the forearms. Other ingredients, like natural flavoring and hydrolyzed vegetable protein (HVP), also contain glutamate.

* Mycoprotein.

Meat substitute: Quorn brand foods.

It’s made from processed mold (fungus) and is fashioned into imitation meat. A small percentage of people are sensitive to it. Reactions include vomiting, nausea, diarrhea, and, less often, hives and potentially fatal anaphylactic reactions. The FDA has refused to ban the use of mycoprotein or to require foods to bear a warning label about adverse reactions.

* Neotame.

Artificial sweetener: Diet soda, other diet foods.

It’s chemically related to aspartame, but is used at much lower levels. It’s also more stable (unlike aspartame, it can be used in baked foods). Neotame doesn’t appear to be a problem for people with PKU (phenylketonuria).

* Oat Fiber, Wheat Fiber.

Isolated fiber: Cereal, crackers, bread, muffins.

When a food ingredient contains the word “fiber,” it’s code for an isolated fiber. “Wheat fiber” and “oat hull fiber” are insoluble fibers, which may help prevent constipation but don’t lower blood cholesterol or blood sugar. “Oat fiber” can be either insoluble or soluble fiber. Soluble fiber may lower blood cholesterol and blood sugar but doesn’t prevent constipation.

* Olestra (Olean).

Fat substitute: Lay’s Light chips, Pringtes Light chips.

It’s a synthetic fat that isn’t absorbed as it passes through the digestive system, so it has no calories. It can cause severe and incapacitating diarrhea, loose stools, abdominal cramps, and flatulence.

* Oligofructose.

Sweetener, bulking agent, emulsifier, prebiotic: Frozen desserts, cookies, energy andgranola bars.

It’s either synthesized from sucrose or extracted from chicory roots. Like inulin and other soluble fibers, oligofructose is digested by bacteria in the large intestine, but not by human enzymes, and provides only about half the calories of fructose or other sugars. Oligofructose promotes the growth of beneficial bifidus bacteria.

* Partially Hydrogenated Oil.

Fat: Baked goods, fried restaurant food, icing, microwave popcorn, pie crust, shortening, stick margarine.

Vegetable oil can be made into a semisolid shortening or margarine by chemically adding hydrogen. The process creates trans fats, which raise LDL (“bad”) cholesterol and lower HDL (“good”) cholesterol, making them worse for your heart than saturated fat.

* Phosphates, Phosphoric Acid.

Acidulant, buffer, chelating agent, color stabilizer, emulsifier, nutrient: Baked goods, breakfast cereal, cheese, cured meat, dehydrated potatoes, powdered food, soda.

While excessive consumption of phosphates may contribute to osteoporosis, only a small fraction of the phosphates in the diet comes from additives.

* Phytosterols or Phytostanols.

Cholesterol-lowerers: Margarine (Benecol, Take Control), added to some orange juices and breads.

Plant sterols (or stanols) are found naturally in many nuts, seeds, vegetable oils, fruits, vegetables, and other foods. High doses can reduce the absorption of cholesterol from food, which can lower LDL (“bad”) cholesterol levels by 10 to 15 percent. They may also slightly reduce the absorption of carotenoids.

* Polydextrose.

Bulking agent: Reduced-calorie salad dressing, baked goods, candies, pudding, frozen desserts.

Polydextrose is made by combining dextrose (corn sugar) with the sugar alcohol sorbitol. The result is a slightly sweet, reducedcalorie bulking agent. The FDA requires labels of foods that would likely provide more than 15 grams of polydextrose to carry a mild warning: “Sensitive individuals may experience a laxative effect from excessive consumption of this product.”

* Polysorbate 60.

Emulsifier: Baked goods, frozen desserts, imitation cream.

Polysorbate 60 and its close relatives, polysorbate 65 and polysorbate 80, work like mono- and diglycerides. They keep baked goods from going stale, keep dill oil (a flavoring) dissolved in bottled dill pickles, help coffee creamers dissolve, and prevent oil from separating in artificial whipped cream.

* Potassium Bromate.

Dough strengthened White flour.

Most bromate rapidly breaks down to form innocuous bromides. However, bromate itself causes cancer in animals, and the tiny amounts that may remain in bread pose a small risk. Bromate was banned in the United Kingdom in 1989 and it isn’t used in California (probably because foods made with it would have to carry a cancer warning).

* Propyl Gallate.

Antioxidant, preservative: Chewing gum, chicken soup base, meat, potato sticks, oil.

It helps prevent fats and oils from spoiling and is often used together with BHA and BHT. The best animal studies hinted that it might cause cancer.

* Quinine.

Flavoring: Bitter lemon, quinine water, tonic water.

Quinine has been poorly tested as a food additive, and there’s a slight chance that it causes birth defects, so pregnant women should avoid it.

* Saccharin.

Artificial sweetener: No-sugar-added foods, tabletop sweetener (Sweet’N Low).

Animal studies have shown that it can cause cancer of the bladder, uterus, ovaries, skin, and other organs. It also appears to increase the potency of other cancer-causing chemicals. A National Cancer Institute study found that heavy-saccharin users had higher rates of bladder cancer than people who used smaller amounts.

* Salt (Sodium Chloride).

Flavoring, preservative: Most processed foods.

It’s probably the single most harmful substance in the food supply. In most people, a diet high in sodium increases blood pressure, which raises heart disease risk.

* Sodium Benzoate, Benzoic Acid.

Preservative: Carbonated drinks, fruit juice, pickles.

It appears to be safe, though sensitive people may experience hives, asthma, or other allergic reactions. Sodium benzoate may also exacerbate hyperactivity in some children. When sodium benzoate is used in acidic beverages that also contain ascorbic acid (vitamin C), the two can form small amounts of benzene, which causes leukemia and other cancers. Under threat of a lawsuit, the leading soft-drink makers recently reformulated their beverages-typically fruit-flavored drinks-to prevent the reaction.

* Sodium Carboxymethylcellulose (CMC).

Thickening and stabilizing agent: Beer, candy, diet foods, ice cream, icing, pie filling.

Among other things, it keeps sugar from crystallizing.

* Sodium Nitrate, Sodium Nitrite.

Coloring, flavoring, preservative: Bacon, corned beef, frankfurters, ham, luncheon meat, smoked fish.

Sodium nitrite stabilizes the red color in cured meat and adds flavor. Without it, hot dogs and bacon would look gray. It also helps prevent the growth of bacteria that cause botulism. Adding nitrite to food can create small amounts of potent cancercausing chemicals called nitrosamines, particularly in fried bacon. Companies now add ascorbic acid or erythorbic acid to bacon to keep nitrosamines from forming. While nitrate and nitrite introduce only a small cancer risk, they’re still worth avoiding.

* Sorbic Acid, Potassium Sorbate.

Prevents mold: Cake, cheese, dried fruit, jelly, syrup, wine.

Sorbic acid occurs naturally in many plants.

* Sorbitan Monostearate.

Emulsifier: Cake, candy, pudding, icing.

Like mono- and diglycerides and polysorbates, it keeps oil and water from separating. In chocolate candy, it prevents the discoloration that normally occurs when the candy is warmed up and then cooled.

* Sorbitol.

Maintains moisture; sweetener, thickening agent: Diet drinks, no-sugar-added candy and chewing gum.

It’s a sugar alcohol that occurs naturally in fruits and is a close relative of sugar, though it’s half as sweet. Because bacteria don’t metabolize sorbitol well, it’s used in no-sugar-added chewing gum, which doesn’t cause tooth decay. Some diabetics use sorbitol-sweetened foods because it’s absorbed slowly and doesn’t cause blood sugar to increase rapidly. Moderate amounts of sorbitol may have a strong laxative effect, but otherwise it’s safe.

* Starch, Modified Starch.

Thickening agent: Baby food, gravy, soup.

It’s used in many foods as a thickening agent and to keep solids suspended. Chemists can “modify” it with certain chemicals to make it dissolve in cold water. Starch and modified starches sometimes replace nutritious ingredients like fruit. One preliminary study indicated that modified starches can cause diarrhea in infants.

* Stevia.

Natural sweetener: Dietary supplement.

Small amounts are probably safe. High doses fed to rats reduced sperm production and increased cell proliferation in their testicles, which could cause infertility or other problems. Stevia can only be sold in the United States as a dietary supplement, but several companies are reportedly developing a steviaderived sweetener and plan to seek approval from the FDA to use it in foods.

* Sucralose.

Artificial sweetener: No-sugar-added baked goods, frozen desserts, ice cream, soft drinks, tabletop sweetener (Splenda).

Unlike aspartame, sucralose can be used in baked foods. It appears to be the safest artificial sweetener, though no independent tests have been conducted.

* Sugar (Sucrose).

Sweetener: Sweetened food, table sugar.

Sucrose (table sugar) occurs naturally in fruit, sugar cane, and sugar beets. Sugar, corn syrup, and other refined sweeteners make up about 15 percent of the average person’s diet, but provide no vitamins, minerals, fiber, or protein. Sucrose and other refined sugars can promote obesity, tooth decay, and-in people with high triglycerides-heart disease.

* Sulfites (Sodium Bisulfite, Sulfur Dioxide).

Bleach, preservative: Dried fruit, processed potatoes, shrimp, wine.

Sulfiting agents prevent discoloration (in dried fruit, some fresh shrimp, and some dried, fried, or frozen potatoes) and bacterial growth (in wine). They also destroy vitamin B-1. Sulfites can cause severe reactions in sensitive people, especially those with asthma.

* Thiamin Mononitrate.

Vitamin B-1: Enriched flour, fortified cereal.

It’s perfectly safe.

* Vanillin, Ethyl Vanillin.

Substitute for vanilla: Baked goods, beverages, candy, chocolate, frozen desserts, gelatin.

Vanilla flavoring is derived from a bean, but vanillin, the major flavor component of vanilla, is cheaper to produce in a factory. A derivative, ethyl vanillin, comes closer to matching the taste of real vanilla.

* Xylitol.

Sweetener: Sugar-free chewing gum, low-calorie foods.

Like other sugar alcohols (maltitol, mannitol, sorbitol), xylitol is not well absorbed by the body, so it has fewer calories than table sugar. And it doesn’t promote tooth decay. Large amounts may have a laxative effect.

(C) 2008 Nutrition Action Health Letter. via ProQuest Information and Learning Company; All Rights Reserved

MM Updates 6-12-08

J&J Recalling Certain Lots of Drugs After Theft
Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
NEW YORK (Reuters) May 15 – Johnson & Johnson said on Thursday it was voluntarily recalling specific lots of three of its medications to protect patients from receiving potentially mishandled or damaged products after a truck carrying the drugs was stolen.
The truck, which was stolen earlier this month while en route from a distribution center in Kentucky to a specialty distributor, was carrying the anemia treatment Procrit, the rheumatoid arthritis drug Remicade, and the chemotherapeutic agent Doxil.
The theft was reported to local and federal law enforcement offices, as well as to the U.S. Food and Drug Administration, but the transport trailer and products have not been recovered, the company said.
J&J units Centocor and Ortho Biotech have recalled just the products with lot numbers that match those that were on the stolen truck.
“If the stolen product were to be reintroduced into distribution channels, the companies cannot guarantee that products were stored at appropriate temperatures, nor can the companies guarantee the products were not damaged,” J&J said in a statement.
“A voluntary withdrawal of products with lot numbers corresponding to that of the stolen product minimizes the possibility of inadvertent use of stolen product by physicians and, therefore, the overall risk to patients,” it said.
The amount of stolen and withdrawn product represents a very small proportion of the total product within the distribution channel, J&J said, adding that it does not expect a disruption in product availability for patients.
The companies discontinued shipment of products with lot numbers matching the stolen products on May 7.
Health-care providers and patients who received those drugs from an authorized distributor on or before May 7 should consider the product safe for use, J&J said.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
 

Misdiagnoses Caused in Part by Overconfidence
Salynn Boyles
WebMD Health News 2008. © 2008 WebMD Inc.
April 30, 2008 — Most of the time a medical diagnosis is on point. But misdiagnoses do occur, and an overly confident doctor may be partly to blame, a new review suggests.
The rate of diagnostic error is as high as 15%, Eta S. Berner, EdD, and Mark L. Graber, MD, write in a special edition of The American Journal of Medicine dedicated to understanding and addressing diagnostic errors.
Physician overconfidence and a lack of feedback following a diagnosis are two important contributors to the problem, they note.
“When directly questioned, many clinicians find it inconceivable that their own error rate could be as high as the literature demonstrates,” Berner and Graber write. “They acknowledge that diagnostic error exists, but believe the rate is very low, and that any errors are made by others who are less skillful or less careful.”
Berner says it is often the cases physicians perceive as routine and unchallenging that end up being misdiagnosed.
“With the hard cases, doctors generally seek out different opinions or turn to (computer-based) decision support tools,” she tells WebMD.
A Missed Diagnosis
Retired engineer Paul Mongerson is all too aware of the problem of medical misdiagnosis, and he has spent the last 28 years addressing the issue.
In 1980, Mongerson was incorrectly told by four different doctors that he had pancreatic cancer, a highly deadly cancer that kills most people who have it within five years.
Mongerson made up a matrix charting his symptoms and test results to help him assess the probability that his doctors were right.
“I determined from that matrix that I didn’t have cancer,” he tells WebMD.
Just two days before he was scheduled for cancer surgery, a fifth doctor agreed and Mongerson canceled the operation.
“I said at the time that if I survived I was going to see what I could do to help other people,” he says.
What Mongerson did was form a foundation to fund the development of computer-based programs designed to assist physicians in diagnosing disease.
While such programs are being used in many hospital and educational settings, they are not yet widely used by private practice physicians.
Mongerson says performing more autopsies and having systems in place to crosscheck medical diagnoses would help address the issue of lack of feedback.
Barriers to Patient Follow-up
In one of the newly published essays, Gordon D. Schiff, MD, of Chicago’s Cook County Hospital addressed the barriers to the follow-up of patients in the real-world, clinical practice setting.
Not surprisingly, lack of time was at the top of his list, followed by fragmentation of care, the large number of symptoms for which there is no clear diagnosis, cost and managed care barriers, and physician defensiveness about critical feedback from peers.
“Learning and feedback are inseparable,” Schiff writes. “The old tools (used by physicians) — individual idiosyncratic systems to track patients, reliance on human memory, and patient adherence to or initiating of follow-up appointments — are too unreliable to be depended upon to ensure high quality in modern diagnosis.”
He calls for a systematic approach to link diagnoses with patient outcomes.
In a different essay, Mark Graber, MD, of the department of medicine at State University of New York at Stony Brook and VA Medical Center in Northport, N.Y., proposes new roles for patients that can help. One is to have the patient become a “watchdog for cognitive errors” by having doctors communicate to patients more about what diagnoses they are considering rather than just telling patients what tests to get or what medications to take. Sharing more information with patients can help patients be more active in checking for errors.
A second role is as a “watchdog for system-related errors” to help keep track of their own medical information such as test results and medication lists. By doing so, “the patient can play a valuable role in combating errors related to latent flaws in our healthcare systems and practices,” Graber writes.
Berner adds that patients can help by questioning their doctors carefully during the diagnostic process, and, especially, letting them know when they might have made the wrong call.
“If your doctor says you should be better in a week, and you aren’t, call the office and let them know,” she says, adding that a surprising number of patients do not do this.
Patients who aren’t sure about their diagnosis should also ask their doctors what else their condition might be, she says.
The simple suggestion was a major focus of the best-selling 2007 book How Doctors Think by Harvard Medical School physician Jerome Groopman.
In it Groopman writes that instead of being intimidated by their doctors, patients should ask questions like, “Is there anything that doesn’t fit your diagnosis?” and “Is it possible that I may have more than one problem?”
Mongerson tells WebMD that the point is not to put physicians on the defensive, but to explore all medical possibilities.
“After everything I went through I am still very high on doctors,” he tells WebMD. “They are very dedicated people who work very hard and go through hell when they find out they have made a mistake. The problem is, they don’t normally find out.”
SOURCES:
Berner, E.S. The American Journal of Medicine, supplemental issue, May 2008; vol 121.
Eta S. Berner, EdD, professor, department of health services administration, University of Alabama at Birmingham.
Gordon D. Schiff, MD, Cook County Hospital, Chicago.
Paul Mongerson, retired engineer; founder, Paul Mongerson Foundation, Naples, Fla.
Groopman, J. How Doctors Think, Houghton Mifflin, 2007.
Graber, M. The American Journal of Medicine, supplemental issue, May 2008, vol 121.
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Zoledronic Acid-Thalidomide Combination Does Not Increase Renal Risk

Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
By Will Boggs, MD
NEW YORK (Reuters Health) May 01 – Maintenance therapy with zoledronic acid and thalidomide in patients with multiple myeloma does not increase the risk of renal impairment, according to a report posted on March 31st by BMC Clinical Pharmacology.
“There is no evidence for a pharmacokinetic or clinically relevant interaction between these two drugs,” Dr. Andrew Spencer from The Alfred Hospital, Prahan, Victoria, Australia told Reuters Health.
Previous case reports suggested that multiple myeloma patients receiving thalidomide for disease control along with zoledronic acid for bone maintenance faced higher risks of renal impairment than patients receiving other treatments, the authors explain.
In response to a request by the U.S. Food and Drug Administration to Novartis — the manufacturer of zoledronic acid (Zometa) — Dr. Spencer and colleagues sought to determine whether there were significant pharmacokinetic interactions between zoledronic acid and thalidomide and to monitor renal safety of multiple myeloma patients receiving both drugs.
Mean maximal plasma concentrations and mean plasma concentrations over 24 hours for zoledronic acid did not differ significantly when the drug was administered with or without thalidomide, the authors report.
Similarly, the researchers note, mean serum creatinine values did not differ significantly after up to 16 infusions of zoledronic acid between patients treated with or without thalidomide.
“The alleged adverse interaction claimed by some, based on case reports, is clearly not confirmed,” Dr. Spencer concluded.
Furthermore, “The Australasian Leukaemia and Lymphoma Group (ALLG) MM6 trial (thalidomide, prednisolone, Zometa versus prednisolone, Zometa) that is presently submitted for publication showed no difference whatsoever in the incidence of renal adverse events between the two arms,” he added.
BMC Clin Pharmacol 2008;8.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Acrylamide May Increase Cancer Risk

Salynn Boyles
WebMD Health News 2008. © 2008 WebMD Inc.
May 14, 2008 — The chemical acrylamide — found in French fries, potato chips, and even bread and coffee — is known to cause cancer in animal studies. Now new research from the Netherlands suggests that it may do the same in humans.
Acrylamide is used in the manufacture of cosmetics, plastics, and food packaging. Until just a few years ago, cigarette smoke and occupational exposures were considered the main sources of exposure to the compound.
But in 2002, researchers in Sweden reported that the chemical is also present in certain foods, especially starchy foods that are fried or baked.
Even black olives and breakfast cereals have some acrylamide, University of Southern California professor and nutrition expert Roger Clemens, DrPH, tells WebMD.
“It is clear that our foods have contained this compound since man started cooking with fire,” he says.
Acrylamide and Cancer
What is less clear is whether dietary exposure to acrylamide poses a health risk.
In an effort to address this question, researchers from Maastricht University in the Netherlands examined data from a large Dutch study on diet and cancer begun in 1986.
Almost 121,000 participants between the ages of 55 and 70 completed a detailed food-frequency questionnaire designed to determine their eating habits. The answers, combined with a separate database, were used to estimate acrylamide intake.
For this study, the researchers focused on acrylamide intake and cancers of the kidney, bladder, and prostate. After a follow-up of 13 years, there were 339 cases of kidney cancer, 1,210 cases of bladder cancer, and 2,246 cases of prostate cancer.
On average, people in the study ate about 22 micrograms of acrylamide a day. To put this amount in perspective, a 2.5-ounce serving of French fries contains about 25 micrograms of the chemical.
The participants were divided into five categories of acrylamide consumption. People who ate the highest amounts of the chemical were found to have a 59% greater risk for kidney cancer than those who ate the least, researcher Janneke G. Hogervorst tells WebMD.
The risk appeared to be especially strong for smokers.
Acrylamide consumption did not appear to be associated with an increased risk for cancers of the bladder or prostate.
In findings reported last year using the same database and study design, Hogervorst and colleagues reported that postmenopausal, nonsmoking women whose diets included the most acrylamide had significantly increased risk for ovarian and endometrial cancer than women whose diets contained the least.
That study was published last December in the journal Cancer Epidemiology Biomarkers and Prevention. The latest findings appear in the May issue of the American Journal of Clinical Nutrition.
“In the future we hope to look at many more cancer types,” Hogervorst says. “We also hope that other researchers will do similar studies to expand on our research.”
Acrylamide in U.S. Diet
But a critic of that research tells WebMD that the Dutch studies and those of similar design do little more than confuse the public.
“They went looking for an association in this study and they found one,” says Jeff Stier. “But people should not confuse association with causation.”
Stier is associate director of the American Council on Science and Health, a consumer education group.
The FDA has reported that 100% of Americans consume acrylamide, but exposure levels do not appear to be increasing.
Clemens, who is a spokesman for the American Society for Nutrition, points out that estimates by the FDA and the World Health Organization suggest that typical dietary exposures do not come close to the exposures that were shown to cause tumors in lab animals.
“The exposures in the animal studies were [the equivalent] of about 300 times the amount that a typical person would consume,” he says.
He adds that there are still plenty of good reasons for limiting French fries and potato chips, noting that “balance, moderation and variety are the keys to a healthful lifestyle.”
SOURCES:
Hogervorst, J.G. American Journal of Clinical Nutrition, May 2008; vol 87: pp 1428-1438.
Janneke G. Hogervorst, doctoral candidate, Maastricht University, Maastricht, Netherlands.
Roger Clemens, DrPH, professor, University of Southern California; spokesman, American Society of Nutrition.
Jeff Stier, associate director, American Council on Science and Health.
Hogervorst, J.G. Cancer Epidemiology Biomarkers & Prevention, November 2007; vol 16: pp 2304-2313.
FDA/CFSAN: “2006 Exposure Assessment for Acrylamide.”
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Outlook Relatively Favorable for Younger Myeloma Patients
 
Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
By Will Boggs, MD
NEW YORK (Reuters Health) May 12 – Myeloma patients younger than 50 years present with more favorable features and have better survival than older myeloma patients, according to a report in the April 15th Blood.
“In cancer, younger age frequently is associated with better outcome, with the exception of breast cancer where patients below age 35 do much worse,” Dr. Heinz Ludwig from Wilhelminenspital, Vienna, Austria told Reuters Health. “However, the very high 10-year survival rate of 44% in patients aged 40 or younger after stem cell transplantation was surprising.”
Dr. Ludwig and colleagues report the presenting features and outcomes after conventional and high-dose therapy in 10,549 patients with multiple myeloma, including 1689 patients younger than 50 years of age.
Younger patients were more likely than older patients to have better ECOG performance status and less advanced ISS stage and were less likely to have adverse prognostic factors, the authors report. The same was true of patients younger than 40 years of age.
Median adjusted survival was higher for the younger patients (5.2 years) than for the older patients (3.7 years), the report indicates.
Ten-year survival after conventional treatment was significantly higher in the younger patients (19%) than in the older patients (8%), the investigators say, as was 10-year survival after high-dose chemotherapy with autologous stem cell transplantation (43% versus 29%, respectively).
“Even before the introduction of the novel drugs bortezomib and lenalidomide, an improvement in survival was obtained in conventionally treated patients in the enrollment period 1992-2002 as compared to earlier enrollment periods,” Dr. Ludwig said. “This seems partly due to the introduction of thalidomide, better supportive care, higher usage of transplantation, and stage migration at diagnosis.”
Risk factors at presentation improved significantly since the early 1980s, the researchers note, especially among patients aged 50 years and older.
“Lower ISS stage is the most important prognostic factor when a series of clinical parameters are evaluated,” Dr. Ludwig explained.
“Transplantation proved to be superior in patients of all age groups eligible for transplantation compared to those treated with conventional therapy,” Dr. Ludwig concluded. “Autologous stem cell transplantation should be used in patients who are eligible for this procedure.”
Blood 2008;111:4039-4047.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Lenalidomide Raises Clot Risk in Multiple Myeloma Patients
 
Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
NEW YORK (Reuters Health) May 08 – Thromboembolic events are increased in patients undergoing lenalidomide-based therapy for multiple myeloma, US and Italian researchers report. Aspirin prophylaxis appears to reduce this risk.
“There is a real risk of blood clots with the use of lenalidomide in myeloma,” investigator Dr. S. Vincent Rajkumar told Reuters Health, “particularly in combination with other chemotherapeutic drugs.”
To investigate these and other risk factors, Dr. Rajkumar of the Mayo Clinic College of Medicine, Rochester, Minnesota and colleagues conducted a pooled analysis of data from three clinical trials involving 125 patients who had previously untreated multiple myeloma.
Along with lenalidomide-based therapy, 52 received high-dose dexamethasone (40 mg 12 days a month) and 73 received prednisolone or dexamethasone 40 mg, 4 times per month. In addition, 110 were given thromboprophylactic treatment, primarily aspirin.
Overall, 10 patients (8%) developed deep vein thrombosis (DVT), the investigators report in the April 1st issue of Cancer. Four were not receiving thromboprophylactic treatment at the time of the event.
There was no significant difference in the incidence of DVT in patients receiving concomitant erythropoietin therapy and those not receiving this treatment. The rate of DVT was higher in the high-dose corticosteroid group compared with the low-dose group (12% versus 6%, respectively), but this difference did not reach statistical significance.
The rate of thrombosis was lower than the range reported in the literature, the investigators point out, possibly because most patients were receiving anticoagulant prophylaxis and 58% received low-dose corticosteroid.
“The best prophylaxis,” Dr. Rajkumar concluded, “should take into account all the risks and benefits. By using a low dose of steroids, and using aspirin as a preventive measure, the risk of blood clots can be minimized to less than 10%.”
Cancer 2008;112:1522-1528.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

US Oncology Physician Network Calls for Full Coverage of PET
Allison Gandey
Medscape Medical News 2008. © 2008 Medscape
May 19, 2008 — Results from the national oncologic positron emission tomography (PET) registry are considered landmark, and specialists are now using these findings to support broader national coverage for the imaging technique. Study investigators have submitted a formal request to the US Centers for Medicare and Medicaid Services (CMS), asking that PET be considered for wider use. The US Oncology physician network is backing this request and asking CMS to end data-collection requirements.
In 2005, the CMS established a new approach, called coverage with evidence development, for selected promising technologies. The new policy provided a novel, formal approach for coverage of evolving diagnostic and treatment methods that would not otherwise meet evidentiary standards for Medicare.
PET was among the first technologies to be covered under this policy. The national oncologic PET registry was subsequently developed to assess the way PET affects decision-making.
PET with 18F-fluorodeoxyglucose (FDG) is based on the observation that most cancers demonstrate higher glucose use than normal tissues. Lead investigator Bruce Hillner, MD, from the Virginia Commonwealth University in Richmond, says the new registry shifts the research focus from test performance to the impact of a specific test on patient-care decisions.
Clinicians Changed Intended Care After Seeing Scan Results
Initial results from the registry were published in the May 1 issue of the Journal of Clinical Oncology. As reported by Medscape Oncology when the findings were released online, researchers found that clinicians changed the intended care of more than 1 in 3 cancer patients as the result of PET-scan findings.
“This is a good example of cooperation between the professional sector and government to get to the truth,” Steven Larson, MD, from the Memorial Sloan-Kettering Cancer Center in New York, writes in an accompanying editorial.
The registry included data from more than 22,900 studies of elderly patients from 1178 centers. This represents nearly 80% of all PET centers in the United States. Researchers collected questionnaire data from referring physicians on intended patient management before and after PET scans.
“We were surprised by the impact of PET on patients with a pre-PET intended management of biopsy,” the investigators noted in their report.
“This study has major strengths, particularly in its scale,” Dr. Larson adds. “This is no small feat, and reflects the power of Medicare data when used for this type of focused clinical trial.”
Study Represented Nearly 80% of All American PET Centers
The main limitation of this study is probably in the primary end point — intended patient management rather than the actual management, the editorialist notes. “There is also no certainty that the management proposed is correct.”
Although it is not the role of diagnostic tests to dictate a management plan, he writes, there can be no doubt from the study that statistically PET had a major impact on primary physicians’ intended management across the spectrum of clinical sites and practicing caregivers.
“Still, on the basis of the strong message from this study and CMS’s role in planning,” Dr. Larson suggests, “it seems likely that the indications for PET in oncology will be broader in the future. In this way, this study is an important step in the long process of establishing clinical acceptance and insurance reimbursement for PET as a routine diagnostic imaging modality.”
The US Oncology physician network is also recommending that PET be considered for broader use. Its network has facilities across the country and of the 1598 sites in the registry study, 61 were US Oncology practices.
Could the Scans Become a Routine Diagnostic?
The findings confirm the expectation that PET is clinically useful in a very broad spectrum of tumor types, the network stated in a letter to CMS in May. Signed by Landis Griffeth, MD, the national medical director for PET for US Oncology and director of nuclear medicine at the Baylor University Medical Center in Dallas, Texas, the letter urges CMS to end the coverage-with-evidence requirements for PET.
“Continuing these requirements could prevent many patients from receiving optimal care for their cancer resulting in increased morbidity and mortality,” Dr. Griffeth writes. “The decision to use FDG-PET for oncologic imaging should be left to treating physicians working in consultation with imaging specialists and with their patients.”
CMS is currently reviewing the request.
Dr. Bruce Hillner reports having financial ties to the Academy for Molecular Imaging. Coauthor Dr. Barry Siegel, reports having financial ties to the Radiology Corporation of America, Dynamics, Cardinal Health, Siemens, Nikon Medi-Physics, DMS Imaging, PETNET Radiopharmaceuticals, Eastern Isotopes, General Electric, and Philips. Senior author R. Edward Coleman reports having financial ties to the Radiology Corporation of America, General Electric, Cardinal Health, and Siemens. Editorialist Dr. Steven Larson reports having financial ties to Cellectar, GE Medical Systems, Philips, and CTI Siemens; and having received research funding from the National Cancer Institute, the Department of Energy, the Department of Defense, GE Medical Systems, and Genentech.
J Clin Oncol. 26:2155-2161 Abstract and 2083-2084 Abstract.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Reduced Cancer Risk Seen With Statin Use
Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
NEW YORK (Reuters Health) May 15 – High-dose lipophilic statin use is associated with a significant reduction in the incidence of cancer, according to results of a study published in the April issue of the American Journal of Medicine.
Antitumorigenic effects for statins have been proposed, “although original reports had actually suggested the potential opposite, procarcinogenic effects of statins,” Dr. Louise Pilote, of McGill University, Montreal, Canada, and colleague write. “Despite massive amounts of data, the issue remains inconclusive.”
In a retrospective observational study, the researchers examined the association between lipophilic statin use and cancer occurrence in over 30,000 patients discharged from the hospital after admission for acute MI in the province of Quebec. The team linked the Quebec hospital discharge summary database to the drugs claims database.
The researchers defined high-dose statin use as a filled prescription, within 3 days after hospital discharge, at or above the statin-specific target dose, for any of the lipophilic statin medications (atorvastatin, simvastatin, lovastatin, or fluvastatin). Low-dose statin use was defined as a filled prescription, within 3 days after discharge, below the statin-specific target dose.
Overall, 1099 subjects were hospitalized with a cancer diagnosis during follow-up for up to 7 years.
The overall crude incidence rates of hospitalizations for cancer were 13.9, 17.2, and 20.6 per 1000 person-years among statin high-dose users, low-dose users, and non-users, respectively. The adjusted hazard ratios for high-dose statin use and low-dose statin use were 0.75 and 0.89 versus non-use, respectively.
“This is the first study to suggest a dose-response effect of lipophilic statins on cancer occurrence,” Dr. Pilote’s team notes. “Future studies should provide additional evidence allowing the assessment of long-term effects of statins on cancer risk.”
Am J Med 2008;121:302-309.
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

Antioxidants May Compromise Cancer Therapy
Reuters Health Information 2008. © 2008 Reuters Ltd.
Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
NEW YORK (Reuters Health) May 27 – A review of randomized trial data suggests that cancer patients should avoid the routine use of antioxidant supplements as they may diminish the efficacy of chemotherapy and radiation.
Still, findings from different studies are conflicting and, therefore, further research is warranted to determine whether antioxidants can be safely given during cancer therapy and whether any benefit is seen.
Although research looking at antioxidant use during cancer therapy has been on-going on for nearly two decades, it remains a controversial topic, lead author Dr. Brian D. Lawenda, from the Navel Medical Center in San Diego, California, and colleagues point out in the May 27th online issue of the Journal of the National Cancer Institute.
In investigating the impact of antioxidant use on radiotherapy, the researchers identified nine relevant studies, including two meta-analyses. Only three of the studies, however, were randomized controlled trials that specifically addressed the topic.
Results from the largest of the three trials suggested that antioxidant therapy reduced overall survival. However, there is evidence indicating that one antioxidant agent, amifostine, can protect certain healthy tissues from radiologic damage without increasing resistance in cancerous tissue.
Sixteen trials, including six that were placebo-controlled, were identified that looked at the effects of antioxidant supplementation on chemotherapy. There was no evidence that antioxidant use reduced treatment response rates, although the authors warn that none of the studies were really large enough to address this properly.
“Despite some intriguing studies that have suggested the benefit of adjunctive antioxidant treatments in cancer patients, the totality of the available evidence is equivocal at best and leaves us with serious concerns about the potential for harm,” Dr. Lawenda’s team concludes.
J Natl Cancer Inst 2008;100:1-11.

MM Updates 6-11-08

Development and validation of a predictive model for chemotherapy-associated thrombosis
Alok A. Khorana1, Nicole M. Kuderer2, Eva Culakova2, Gary H. Lyman2, and Charles W. Francis1
1 James P. Wilmot Cancer Center and the Department of Medicine, University of Rochester, NY; and 2 Duke University Medical Center and the Duke Comprehensive Cancer Center, Durham, NC
Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 109/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 109/L, and body mass index of 35 kg/m2 or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for studies of thromboprophylaxis.
Development and validation of a predictive model for chemotherapy-associated thrombosis
Alok A. Khorana1, Nicole M. Kuderer2, Eva Culakova2, Gary H. Lyman2, and Charles W. Francis1
1 James P. Wilmot Cancer Center and the Department of Medicine, University of Rochester, NY; and 2 Duke University Medical Center and the Duke Comprehensive Cancer Center, Durham, NC
Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association of VTE with multiple variables was characterized in a derivation cohort of 2701 cancer outpatients from a prospective observational study. A risk model was derived and validated in an independent cohort of 1365 patients from the same study. Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 109/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 109/L, and body mass index of 35 kg/m2 or more (1 point each). Rates of VTE in the derivation and validation cohorts, respectively, were 0.8% and 0.3% in low-risk (score = 0), 1.8% and 2% in intermediate-risk (score = 1-2), and 7.1% and 6.7% in high-risk (score 3) category over a median of 2.5 months (C-statistic = 0.7 for both cohorts). This model can identify patients with a nearly 7% short-term risk of symptomatic VTE and may be used to select cancer outpatients for sBH3-only proteins Noxa, Bmf, and Bim are necessary for arsenic trioxide–induced cell death in myeloma
Alejo A. Morales1, Delia Gutman1, Kelvin P. Lee2, and Lawrence H. Boise1
1 Microbiology and Immunology and The Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, FL; and 2 Department of Immunology and Medicine, Roswell Park Cancer Institute, Buffalo, NY
The use of arsenic trioxide (ATO) to treat multiple myeloma (MM) is supported by preclinical studies as well as several phase 2 studies, but the precise mechanism(s) of action of ATO has not been completely elucidated. We used gene expression profiling to determine the regulation of apoptosis-related genes by ATO in 4 MM cell lines and then focused on Bcl-2 family genes. ATO induced up-regulation of 3 proapoptotic BH3-only proteins (Noxa, Bmf, and Puma) and down-regulation of 2 antiapoptotic proteins Mcl-1 and Bcl-XL. Coimmunoprecipitation demonstrated that Noxa and Puma bind Mcl-1 to release Bak and Bim within 6 hours of ATO addition. Bak and Bim are also released from Bcl-XL. Silencing of Bmf, Noxa, and Bim significantly protected cells from ATO-induced apoptosis, while Puma silencing had no effect. Consistent with a role for Noxa inhibition of Mcl-1, the Bad-mimetic ABT-737 synergized with ATO in the killing of 2 MM lines. Finally, Noxa expression was enhanced by GSH depletion and inhibited by increasing GSH levels in the cells. Understanding the pattern of BH3-only protein response should aid in the rational design of arsenic-containing regimens.
The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1,514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention
David E Gerber, Jodi B Segal, M. Yair Levy, Joyce Kane, Richard J. Jones, and Michael B Streiff*
Hematology-Oncology / Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
General Internal Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States
Hematologic Malignancies / Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
Oncology Data Quality Assurance / Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, United States
Hematology / Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States
* Corresponding author; email: mstreif@jhmi.edu .
Venous thromboembolism (VTE) is increasingly diagnosed among individuals with hematologic malignancies. However, the risk of VTE among patients undergoing hematopoietic stem cell transplantation (HSCT) is unclear. We examined the incidence and risk factors for VTE and bleeding among 1,514 patients undergoing inpatient HSCT. No protocolized VTE prophylaxis was used. By HSCT Day 180, 75 symptomatic VTE events occurred in 70 patients (4.6%; 95% CI, 3.6-5.8%). Fifty-five (3.6%) were catheter-associated, 11 (0.7%) were non-catheter-associated deep venous thromboses, and 9 (0.6%) were pulmonary emboli. Thirty-four percent of VTE events occurred at a platelet count less than 50 K/mm3; 13% occurred at a platelet count less than 20 K/mm3. In multivariate analysis, VTE was associated with prior VTE (OR 2.9; 95% CI, 1.3-6.6) and with graft-versus-host-disease (GVHD) (OR 2.4; 95% CI, 1.4-4.0). Clinically significant bleeding occurred in 230 patients (15.2%; 95% CI, 13.4%-17.1%); 55 patients (3.6%; 95% CI, 2.7%-4.7%) had fatal bleeding. Bleeding was primarily associated with anticoagulation (OR 3.1; 95% CI, 1.8-5.5), GVHD (OR 2.4; 95% CI, 1.8-3.3), and veno-occlusive disease (OR 2.2; 95% CI, 1.4-3.6). In HSCT patients, VTE is primarily catheter-related and three-fold less common than clinically significant bleeding. These findings warrant consideration when selecting VTE prophylaxis in HSCT patients.
Primary cystic lung light chain deposition disease : a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor
Magali Colombat, Herve Mal, Christiane Copie-Bergman, Jacques Diebold, Diane Damotte, Patrice Callard, Michel Fournier, Jean-Pierre Farcet, Marc Stern, and Marie-Helene Delfau-Larue*
APHP, Hopital Tenon, Service d’anatomie pathologique, 7520 Paris, France
APHP, Hopital Bichat, Service de pneumologie, 75018 Paris, France
APHP, Hopital Henri Mondor, Departement de Pathologie, Creteil, F-9400, France
APHP, Hotel Dieu, Service d’anatomie pathologique, 75004, Paris, France
APHP, Hopital Europeen Georges Pompidou, Service d’anatomie pathologique, 75015 Paris, France
AP-HP, Hopital Henri Mondor, Service d’immunologie biologique, INSERM, U841 equipe 9, Universite Paris 12, Faculte de Medecine, Creteil, F-9400, France
Hopital Foch, Service de pneumologie, 92151 Suresnes, France
* Corresponding author; email: marie-helene.delfau@hmn.aphp.fr .
We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in three patients with cystic lung LCDD. Histological examination of the explanted lungs showed diffuse non-amyloid light chain deposits associated with a mild lymphoid infiltrate mainly composed of small CD20+, CD5-, CD10- B lymphocytes arranged in nodules reminiscent of bronchus-associated lymphoid tissue. Using PCR, we identified a dominant B-cell clone in the lung in the three studied patients. The clonal expansion of each patient shared a unmutated antigen receptor variable region sequence characterized by the use of VH4-34 and VK1 gene family with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biological data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.
Thalidomide arm of total therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities
Bart Barlogie*, Mauricio Pineda-Roman, Frits van Rhee, Jeff Haessler, Elias Anaissie, Klaus Hollmig, Yazan Alsayed, Sarah Waheed, Nathan Petty, Joshua Epstein, John D. Shaughnessy Jr., Guido Tricot, Maurizio Zangari, Jerome Zeldis, Sol Barer, and John Crowley
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Cancer Research and Biostatistics, CRAB, Seattle, WA, United States
Celgene Corporation, Celgene Corporation, Summit, NJ, United States
* Corresponding author; email: barlogiebart@uams.edu .
Total Therapy 2 examined the clinical benefit of adding thalidomide up-front to a tandem transplant regimen for newly diagnosed patients with multiple myeloma. When initially reported with a median follow-up of 42mo, complete response rate and event-free survival were superior among the 323 patients randomized to thalidomide whereas overall survival was indistinguishable from that of the 345 patients treated on the control arm. With further follow-up currently at a median of 72mo, survival plots segregated 5 years after initiation of therapy in favor of thalidomide (p=0.09), reaching statistical significance for the one-third of patients exhibiting cytogenetic abnormalities (CA) (p=0.02), a well-recognized adverse prognostic feature. The duration of complete remission was also superior in the cohort presenting with CA such that, at 7 years from onset of complete remission, 45% remained relapse-free as opposed to 20% on the control arm (p=0.05). These observations were confirmed when examined by multivariate analysis demonstrating that thalidomide reduced the hazard of death by 41% among patients with CA-positive disease (p=0.008). As two-thirds of patients without CA have remained alive at 7 years, the presently emerging separation in favor of thalidomide may eventually reach statistical significance as well.
First thalidomide clinical trial in multiple myeloma: a decade later
Frits van Rhee, John D. Shaughnessy, Jr., Elias Anaissie, David Siegel, Antje Hoering, Jerome Zeldis, Bonnie Jenkins, Seema Singhal, Jayesh Mehta, John Crowley, Sundar Jagannath, and Bart Barlogie*
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock
Hackensack University, Hackensack, NJ
Cancer Research and Biostatistics, CRAB, Seattle
Celgene Corporation, Celgene Corporation, Cambridge
Northwestern University, Chicago, IL
St. Vincent’s Hospital, New York, NY
* Corresponding author; email: barlogiebart@uams.edu .
The clinical outcomes of 169 patients, enrolled in the first clinical trial of thalidomide for advanced or refractory myeloma, are updated. Seventeen patients remain alive and 10 event-free, with a median follow-up of 9.2 years. According to multivariate analysis of pre-treatment variables, cytogenetic abnormalities (CA), present in 47% of patients within 3 months of enrollment, and lambda light chain isotype both affected overall survival and event-free survival adversely. Forty percent of the 58 patients lacking these 2 unfavorable features, one-half of whom had no disease recurrence, survived at least 6 years, in contrast to fewer than 5% among those with 1 or 2 risk features (P<0.0001). Patients who had received cumulative thalidomide doses in excess of 42g in the first 3 months enjoyed superior overall and event-free survival. The poor outcome associated with lambda-type myeloma may relate to its over-representation in molecularly defined high-risk disease gleaned from studies in newly diagnosed myeloma.
Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized, controlled trial
Antonio Palumbo*, Sara Bringhen, Anna M Liberati, Tommaso Caravita, Antonietta Falcone, Vincenzo Callea, Marco Montanaro, Roberto Ria, Antonio Capaldi, Renato Zambello, Giulia Benevolo, Daniele Derudas, Fausto Dore, Federica Cavallo, Francesca Gay, Patrizia Falco, Giovannino Ciccone, Pellegrino Musto, Michele Cavo, and Mario Boccadoro
Divisione di Ematologia dell’Universita di Torino, Azienda Ospedaliera S Giovanni Battista, Torino, Italy
Clinica Medica I, Policlinico Monteluce, Perugia, Italy
Cattedra e Divisione di Ematologia, Universita Tor Vergata, Ospedale S Eugenio, Roma, Italy
Unita Operativa di Ematologia Trapianto di Cellule Staminali, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
Divisione di Ematologia, Ospedali Riuniti, Calabria, Italy
Unita Operativa Complessa di Ematologia, Ospedale Sant’Anna di Ronciglione, Ronciglione (VT), Italy
Sezione Medicina Interna e Oncologia Clinica, Policlinico di Bari, Bari, Italy
Divisione di Oncologia ed Ematologia, IRCCS, Candiolo, Italy
Divisione di Ematologia e Immunologia Clinica Universitaria, Dipartimento Medicina Clinica e Sperimentale, Padova, Italy
Ematologia, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
Unita Operativa di Ematologia, Ospedale “A. Businco”, Cagliari, Italy
Istituto di Ematologia, Universita di Sassari, Sassari, Italy
Servizio di Epidemiologia dei Tumori dell’Universita di Torino, Azienda Ospedaliera S. Giovanni Battista e CPO Piemonte, Torino, Italy
Ematologia e Trapianto Cellule Staminali IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy
Istituto di Ematologia e Oncologia Medica, Policlinico S. Orsola, Bologna, Italy
* Corresponding author; email: appalumbo@yahoo.com .
Rationale: The initial analysis of the oral combination melphalan, prednisone, and thalidomide (MPT) in newly diagnosed patients with myeloma showed significantly higher response rate and longer progression-free survival (PFS) than did the standard melphalan and prednisone (MP) combination and suggested a survival advantage. In this updated analysis, efficacy and safety endpoints were updated. Objectives: Patients were randomly assigned to receive oral MPT or MP alone. Updated analysis was by intention-to-treat and included PFS, overall survival (OS), and survival after progression. Findings: After a median follow-up of 38.1 months, the median PFS was 21.8 months for MPT and 14.5 months for MP (P = .0004). The median OS was 45.0 months for MPT and 47.6 months for MP (P = .79). In different patient subgroups, MPT improved PFS irrespective of age, serum concentrations of b2-microglobulin, or high International Staging System. Thalidomide or bortezomib administration as salvage regimens significantly improved survival after progression in the MP group (P = .0002) but not in the MPT group (P = .34). Conclusion: These data confirm activity of MPT for PFS but failed to show any survival advantage. New agents in the management of relapsed disease could explain this finding. The study is registered at ClinicalTrial.gov, number NCT00232934.
 

MM Updates 6-11-08

New Data Support High Complete Remission Rates With VELCADE:  http://sev.prnewswire.com/medical-pharmaceuticals/20080516/NEF04416052008-1.html
 
Bone Pain Can Be A Sign Of Myeloma:  http://www.medicalnewstoday.com/articles/108159.php
 
Thalidomide Plus Dexamethasone: Improved Primary Myeloma Therapy:  http://www.cancerpage.com/news/article.asp?id=12256
 
Two DOXIL(R) Studies to be Presented at American Society of Clinical Oncology (ASCO) Annual Meeting:  http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=109&STORY=/www/story/05-29-2008/0004823065&EDATE=
 
The International Myeloma Foundation Says New Studies Show Longer Survival:  http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20080531005029&newsLang=en
 
New Data from Several Satraplatin Clinical Trials:  http://www.istockanalyst.com/article/viewarticle+articleid_2228631~zoneid_Home~title_New-Data-from-Several.html
 
EntreMed (ENMD) Said ENMD-2076 Demonstrates Antitumor Activity:  http://www.streetinsider.com/FDA/EntreMed+(ENMD)+Said+ENMD 2076+Demonstrates+Antitumor+Activity/3703049.html
EntreMed’s ENMD-2076 Demonstrates Antitumor Activity:  http://www.istockanalyst.com/article/viewarticle+articleid_2242458~title_EntreMed’s-ENMD-2076.html
Seattle Genetics Announces Initiation of SGN-40 Phase Ib Clinical Trial: http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20080602005484&newsLang=en
EntreMed Presents MKC-1 Phase 2 Data at American Society of Clinical Oncology Annual Meeting:  http://www.earthtimes.org/articles/show/entremed-presents-mkc-1-phase-2,417205.shtml
Senesco Expands on Preclinical Multiple Myeloma Findings:  http://www.sunherald.com/447/story/605968.html
Astex Announces New Drug Discovery Alliance with Janssen Pharmaceutica N.V.:  http://www.pharmalive.com/News/index.cfm?articleid=547206&categoryid=15
VIDEO:  AACR Presentation on Myeloma Stem Cell at AACR Meeting:  http://app2.capitalreach.com/esp1204/servlet/tc?cn=aacr&c=10165&s=20385&e=9538&&esptl=700

MM Updates 5-14-08

Use of ultraviolet light irradiated multiple myeloma cells as immunogens to generate tumor-specific cytolytic T lymphocytes:  http://7thspace.com/headlines/279844/use_of_ultraviolet_light_irradiated_multiple_myeloma_cells_as_immunogens_to_generate_tumor_specific_cytolytic_t_lymphocytes.html
 
Firefighter’s cancer battle unites colleagues:  http://www.innisfiljournal.com/innisfiljournal/article/73164
 
ACE-011 Preclinical Data Published in the Proceedings of the National Academy of Sciences:  http://www.pr-inside.com/ace-011-preclinical-data-published-in-r576786.htm
Current and Emerging Drugs Have Not Yet Shown an Advantage in Survival Over Velcade in the Treatment of Relapsed Multiple Myeloma:  http://www.earthtimes.org/articles/show/current-and-emerging-drugs-have,385039.shtml
 
Lenalidomide raises clot risk in multiple myeloma patients:  http://www.curetoday.com/breaking_news/052008/05082008.3.htm
 
Promising research for multiple myeloma:  http://www.wtnh.com/Global/story.asp?S=8311899&nav=menu29_2

Blocking of cancer drug called ‘death by finance’:  http://www.theherald.co.uk/news/news/display.var.2265881.0.Blocking_of_cancer_drug_called_death_by_finance.php
 
Outlook Relatively Favorable for Younger Myeloma Patients:  http://www.cancerpage.com/news/article.asp?id=12210
 
RxTrials Institute Drug Pipeline Alert:  http://fdanews.com/newsletter/article?issueId=11584&articleId=106715
 
Matchmakers: Patients Meet Clinical Trials:  http://online.wsj.com/article/SB121071901838189901.html?mod=googlenews_wsj
 
‘evidence-based medicine’ (EBM):  http://www.cancerdecisions.com/051108.html

MM Update 5-13-08

1: Acta Radiol. 2008 May;49(4):427-35. Links
Comparative study of fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for the detection of spinal bone marrow infiltration in untreated patients with multiple myeloma.
Hur J, Yoon CS, Ryu YH, Yun MJ, Suh JS.
Department of Diagnostic Radiology and Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, South Korea.
BACKGROUND: The presence and extent of osteolytic bone lesions in untreated patients with multiple myeloma are important factors in the staging of the disease, and the extent of bone lesions in multiple myeloma cases significantly influences decisions regarding therapy. Recently, fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) have been used to detect bone marrow involvement in patients with multiple myeloma. PURPOSE: To compare the efficacy of FDG-PET and MRI for the detection of bone marrow infiltration into the spine in untreated patients with multiple myeloma. MATERIAL AND METHODS: Twenty-two patients with multiple myeloma underwent both FDG-PET and spine MRI. The examined spinal regions by MRI included 21 thoracic and lumbar spines, one lumbar spine, and 12 cervical spines. The following imaging sequences were performed: T1-weighted spin-echo MRI with and without fat suppression, and T2-weighted spin-echo MRI in the sagittal plane. In the patients with bone marrow abnormalities, an additional contrast-enhanced T1-weighted spin-echo MR image and a fat-suppressed T1-weighted spin-echo MR image were obtained. Patients were divided into three groups on the basis of the criteria defined by Durie and Salmon: stage I (n=9), stage II (n=3), and stage III (n=10). The number and location of lesions detected in both FGD-PET and MRI were recorded, and the lesions were compared using the McNemar test. Bone marrow biopsy results, the patient’s clinical examinations, and other imaging findings (MRI, FDG-PET, etc.) were used as references. RESULTS: In stages I and II (37 lesions in 12 patients), FDG-PET and MRI detected lesions in 78% (29 of 37 lesions) and 86% (32 of 37 lesions), respectively. However, the difference between the abilities of FDG-PET and MRI to detect lesions was not statistically significant (P=0.317). In stage III (101 lesions in 10 patients), FDG-PET and MRI detected lesions in 80% (81 of 101 lesions) and 92% (93 of 101 lesions), respectively. The difference between the abilities of FDG-PET and MRI to detect lesions was statistically significant (P=0.038). CONCLUSION: MRI is superior to FDG-PET in detecting bone marrow involvement in the spine of patients with advanced multiple myeloma.
PMID: 18415787 [PubMed - indexed for MEDLINE]
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: J Bone Miner Res. 2008 Feb 5 [Epub ahead of print] Links
The Frequency and Risk Factors Associated with Osteonecrosis of the Jaw in Cancer Patients Treated with Intravenous Bisphosphonates.
Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN.
Microabstract We performed a retrospective analysis of 4,019 patients treated with intravenous bisphosphonates to identify the frequency and risk factors associated with osteonecrosis of the jaw (ONJ). ONJ was identified in 29 patients (0.72%), 16 with breast cancer (1.2%) and 13 with multiple myeloma (2.4%). High cumulative doses of bisphosphonates, treatment with zoledronic acid, dental extractions and a history of osteoporosis were identified as significant risk factors.
PMID: 18435574 [PubMed - as supplied by publisher]
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: J Orthop Sports Phys Ther. 2008 Apr;38(4):214. Epub 2008 Mar 31. Links
Thoracic spine compression fracture in a patient with back pain.
Ross MD, Elliott RL.
Department of Physical Therapy, David Grant US Air Force, Travis AFB, CA, USA.
A 55-year-old man was referred to physical therapy because of constant mid-back pain of 1 month’s duration. Because of the strong suspicion for a fracture, thoracic spine anterior-posterior and lateral radiographs were ordered, which revealed compression deformities of the T6, T8, T9, and T12 vertebral bodies. An interventional radiologist ordered magnetic resonance imaging and believed the patient was a candidate for vertebroplasty, a technique in which medical grade cement is injected into a painful fractured vertebral body in an effort to stabilize the fracture. At 1 week following his vertebroplasty the patient was pain free. Further medical evaluation indicated that the patient had underlying osteoporosis, and treatment was initiated. At 1 and 2 years after vertebroplasty, the patient reported being symptom free. However, a history of osteoporosis and multiple compression fractures led to further medical evaluation 2 years after vertebroplasty and the patient was eventually diagnosed with multiple myeloma for which treated was initiated.
PMID: 18434669 [PubMed - in process]
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Cancer. 2008 Apr 23 [Epub ahead of print] Links
Completion of premaintenance phases in total therapies 2 and 3 improves clinical outcomes in multiple myeloma: an important variable to be considered in clinical trial designs.
Barlogie B, Haessler J, Pineda-Roman M, Anaissie E, van Rhee F, Kiwan E, Steward D, Gurley J, Jenkins B, Crowley J.
Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
BACKGROUND.: Total Therapy (TT) programs are complex and their execution over the course of several years is fraught with patient attrition due to failure and toxicity of therapy and patient/physician acceptance. METHODS.: The impact of completion versus noncompletion of intended treatment steps was examined in protocols TT2 (n = 668) and TT3 (n = 303) on overall survival (OS) and event-free survival (EFS). RESULTS.: By using appropriate landmarks of 36 months with TT2 and 18 months with TT3, representing the maxima to completion of premaintenance phases, postconsolidation OS was superior for 211 patients completing versus 311 patients not completing premaintenance steps on TT2 (P = .001), which also pertained to the 161 patients completing versus 47 not completing intended treatment steps on TT3 (P = .01). On multivariate analysis that included all patients, completion of therapy independently favored longer OS and EFS in the context of both standard prognostic factors and gene expression profiling-defined risk; in addition, TT3 prolonged EFS over results obtained with TT2. CONCLUSIONS.: 1) Completion of intended therapy was a significant independent variable conferring superior OS and EFS in TT programs; and 2) after adjusting for completion of therapy, EFS was still superior with TT3 versus TT2, supporting the beneficial role of bortezomib included in TT3. Collectively, these data point to the importance of designing clinical trials that balance the treatment requirements for disease control with host acceptance and tolerance. Cancer 2008. (c) 2008 American Cancer Society.
PMID: 18433012 [PubMed - as supplied by publisher
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: An Med Interna. 2008 Feb;25(2):73-77. Links
[Efficency of bortezomib and dexamethasone in relapsed multiple myeloma treatment: retrospective study in consecutive cases.]
[Article in Spanish]
Khosravi Shahi P, Sabin Domínguez P, Encinas García S, Izarzugaza Perón Y, Pérez Manga G.
Servicio de Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid.
Introduction: Multiple myeloma (MM) is a plasm-cell neoplasm, that is characterized by a monoclonal protein in the serum or urine. Bortezomib is an efficacy drug for the second line treatment of MM. Patients and method: We conducted a retrospective study of 21 consecutive cases with refractory MM treated with bortezomib and dexame-thasone as second line therapy, with the objective of analyzing the overall response rate (primary end point), the progression-free survival (PFS), the overall survival (OS), the duration of response (DR) and toxicity profile (second end points). Results: In our study we found an overall response rate of 70%. With a median follow-up of 15 months, we had a median PFS of 12 months (95% CI: 2-21 months), with a median OS of 17 months (95% CI: 2-32 months), and a median DR of 9 months (95% CI: 5-13 months). Fourty-seven percent of patients had neuropathy, the 33% thrombocytopenia, 13.33% anemia and 26.66% diarrhea. Conclusions: The combination of bortezomib and dexamethasone is an effective and safe treatment in second line of refractory MM, with a manageable toxicity.
PMID: 18432363 [PubMed - as supplied by publisher
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: J Clin Pharm Ther. 2008 Jun;33(3):219-26. Links
Lenalidomide in the treatment of multiple myeloma: a review.
Armoiry X, Aulagner G, Facon T.
Pharmacy Department, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, and Faculty of Pharmacy, Henri Poincaré University, Nancy, France. xavier.armoiry@chu-lyon.fr
Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide.
PMID: 18452408 [PubMed - in process]
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Leuk Lymphoma. 2008 Apr 29;:1-7 [Epub ahead of print] Links
Infectious complications after chemotherapy and stem cell transplantation in multiple myeloma: Implications of Fc gamma receptor and myeloperoxidase promoter polymorphisms.
Mølle I, Ostergaard M, Melsvik D, Nyvold CG.
Department of Hematology, University Hospital of Aarhus, THG, Aarhus, DK-8000, Denmark.
Multiple myeloma is associated with a high risk of infections. We hypothesized that Fc gamma receptor (FCGR) and myeloperoxidase (MPO) promoter gene polymorphisms influence the risk of infections after induction chemotherapy (IC) and autologous stem cell transplantation (ASCT). Retrospectively, we analysed 136 patient courses of IC and 113 procedures of ASCT. Genetic analyses were made with PCR techniques on genomic DNA. The incidence rate ratio of sepsis during ASCT in patients homozygous for the G-129MPO promoter type was 0.30 (95% CI: 0.09-0.96). The G-463AMPO promoter polymorphism was not associated with the risk of infections. The polymorphisms of FCGR2A, FCGR3A and FCGR3B were not convincingly associated with infections. The NA1 variant of FCGR3B was strongly skewed with other risk factors, and the results in IC and ASCT were conflicting. Further studies of the G-129AMPO promoter as a potential risk modifier for infections are relevant.
PMID: 18452102 [PubMed - as supplied by publisher]
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Leuk Lymphoma. 2008 Apr 23;:1-8 [Epub ahead of print] Links
Thalidomide and lenalidomide: Mechanism-based potential drug combinations.
Vallet S, Palumbo A, Raje N, Boccadoro M, Anderson KC.
Division of Hematology and Oncology, Cancer Center, Massachusetts General Hospital, Boston, MA, USA.
Thalidomide and its analogue lenalidomide are potent anti-inflammatory, anti-angiogenic and immunomodulatory drugs, successfully used for the treatment of hematological cancers, in particular multiple myeloma (MM). Both drugs reveal a dual mechanism of action: they target tumour cells by direct cytotoxicity and, indirectly, by interfering with several components of the bone marrow microenvironment. Lenalidomide and thalidomide are versatile drugs with a broad range of activities that potentiate the anti-MM effects of conventional and novel agents. Here, we review the mechanism of action of these drugs, providing a rationale for combination studies in order to improve patient outcome and reduce side effects.
PMID: 18452080 [PubMed - as supplied by publisher]
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Leuk Lymphoma. 2008 Apr 30;:1-10 [Epub ahead of print] Links
The oral PKC-beta inhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines.
Neri A, Marmiroli S, Tassone P, Lombardi L, Nobili L, Verdelli D, Civallero M, Cosenza M, Bertacchini J, Federico M, De Pol A, Deliliers GL, Sacchi S.
Center of Molecular Genetics and Gene Expression, Foundation IRCCS Policlinico, Mangiagalli e Regina Elena.
Deregulation of the protein kinase C (PKC) signalling pathway has been implicated in tumor progression. Here we investigated the PKC inhibitor enzastaurin for its activity against multiple myeloma (MM) cells. Enzastaurin suppresses cell proliferation in a large panel of human myeloma cell lines (HMCLs), with IC(50) values ranging from 1.3 to 12.5 microM and induces apoptosis, which is prevented by the ZVAD-fmk broad caspase inhibitor. These results are consistent with decreased phosphorylation of AKT and GSK3-beta, a downstream target of the AKT pathway and a pharmacodynamic marker for enzastaurin. Furthermore, enzastaurin cytotoxicity is retained when HMCLs were cocultured with multipotent mesenchymal stromal cells. Enzastaurin has additive or synergistic cytotoxic effects with bortezomib or thalidomide. Considering the strong anti-myeloma activity of enzastaurin in vitro and in animal models and its safe toxicity profile, phase II studies in MM patients of enzastaurin alone or in combination with other drugs are warranted.
PMID: 18452078 [PubMed - as supplied by publisher]
enzastaurin (en-zuh-STAW-rin)
 A substance being studied in the treatment of certain types of cancer, including non-Hodgkin lymphoma, breast, colon, lung, ovarian, and prostate. Enzastaurin blocks certain cell signaling pathways, and may prevent the growth of new blood vessels needed for tumors to grow. It is a type of serine threonine kinase inhibitor. Also called enzastaurin hydrochloride and LY317615
 

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Oncol Nurs Forum. 2008 May;35(3):E53-61. Links
Effects of exercise in combination with epoetin alfa during high-dose chemotherapy and autologous peripheral blood stem cell transplantation for multiple myeloma.
Coleman EA, Coon SK, Kennedy RL, Lockhart KD, Stewart CB, Anaissie EJ, Barlogie B.
Colleges of Medicine and Nursing, University of Arkansas for Medical Sciences, Little Rock, USA. colemanann@uams.edu
PURPOSE/OBJECTIVES: To determine the effect of aerobic and strength resistance training and epoetin alfa (EPO) therapy on transfusions, stem cell collections, transplantation recovery, and multiple myeloma treatment response. DESIGN: Randomized clinical trial. SETTING: A myeloma research and therapy center in the south central United States. SAMPLE: 135 patients with multiple myeloma, 120 evaluable. METHODS: Random assignment to exercise or usual care groups. All patients received EPO based on an algorithm. Aerobic capacity, using the six-minute walk test, was assessed prior to induction chemotherapy, prior to stem cell mobilization, and following stem cell collection for all patients and before and after transplantation for patients continuing in the study. Data analysis included analysis of variance to compare other outcome variables by groups. MAIN RESEARCH VARIABLES: Number of red blood cell and platelet transfusions during transplantation, number of attempts at and total number of days of stem cell collection, time to recovery after transplantation, and response to intensive therapy for multiple myeloma. FINDINGS: Recovery and treatment response were not significantly different between groups after transplantation. The exercise group had significantly fewer red blood cell transfusions and fewer attempts at stem cell collection. Serious adverse events were similar in each group. CONCLUSIONS: Exercise with prophylactic EPO therapy reduces the number of RBC transfusions and attempts at stem cell collection for patients receiving intensive treatment for multiple myeloma. IMPLICATIONS FOR NURSING: Exercise is safe and has many physiologic benefits for patients receiving multiple myeloma treatment.
PMID: 18467280 [PubMed - in process]
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Arch Physiol Biochem. 2008 Feb;114(1):71-83. Links
Obesity and cancer: Pathophysiological and biological mechanisms.
Renehan AG, Roberts DL, Dive C.
Department of Surgery, School of Cancer and Imaging Sciences, University of Manchester, Christie Hospital NHS Foundation Trust, Manchester, UK.
Excess body weight (overweight and obesity) is characterized by chronic hyperinsulinaemia and insulin resistance, and is implicated both in cancer risk and cancer mortality. The list of cancers at increased risk of development in an “obesogenic” environment include common adult cancers such as endometrium, post-menopausal breast, colon and kidney, but also less common malignancies such as leukaemia, multiple myeloma, and non-Hodgkin’s lymphoma. The pathophysiological and biological mechanisms underpinning these associations are only starting to be understood. Insulin resistance is at the heart of many, but there are several other candidate systems including insulin-like growth factors, sex steroids, adipokines, obesity-related inflammatory markers, the nuclear factor kappa beta (NF-kappa B) system and oxidative stresses. With such as diversity of obesity-related cancers, it is unlikely that there is a “one system fits all” mechanism. While public health strategies to curb the spread of the obesity epidemic appear ineffective, there is a need to better understand the processes linking obesity and cancer as a pre-requisite to the development of new approaches to the prevention and treatment of obesity-related cancers.
PMID: 18465361 [PubMed - in process]
+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
1: Leuk Lymphoma. 2008 May;49(5):890-5. Links
Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens.
Roussou M, Kastritis E, Migkou M, Psimenou E, Grapsa I, Matsouka C, Barmparousi D, Terpos E, Dimopoulos MA.
Clinical Therapeutics, University of Athens School of Medicine, Alexandra Hospital, Sophias, Greece.
Renal failure is a common feature of multiple myeloma and a major management problem. However there is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents such as bortezomib when administered to newly diagnosed or relapsed/refractory patients with renal failure. PATIENTS AND METHODS: We evaluated 20 consecutive patients with newly diagnosed or relapsed/refractory multiple myeloma and renal failure, defined as a serum creatinine >or= 2 mg/dl. All patients received bortezomib with dexamethasone or in combination with other agents (thalidomide, doxorubicin or melphalan). RESULTS: Reversal of renal failure was documented in 40% of all patients and the median time to reversal was 17 days. Moreover 10 patients (50%) had 50% decrease in serum creatinine and the median time to decrease was 35 days. Some decrease of creatinine was documented in 85% of patients. The objective response rate was 65%. Toxicities were similar to those seen in myeloma patients without renal failure. CONCLUSIONS: Bortezomib based regimens can be administered to myeloma patients with renal impairment and their toxicity and efficacy are similar to those observed in patients without renal impairment. Moreover, bortezomib-based regimens induce improvement of serum creatinine in most patients and reversal of renal failure in approximately one-third.
PMID: 18464107 [PubMed – in process