more questions about anemia drugs

[gdpawel]

EPO is a natural substance made by the kidney. It stimulates the bone marrow to make red blood cells (it is literally a "growth factor"). Healthy adults are usually at about 15 grams a deciliter. When normal people take it, their blood gets too "thick" and they die of heart attacks and strokes.

But it now looks as if increasing the hemoglobin level above 12 is very risky with pharmaceutical EPO. Pharmaceutical EPO makes sludgy blood.

The anemia drugs, which boosts patients' counts of hemoglobin (a protein that carries oxygen in the blood), raise the danger of heart attacks, strokes and death at "high" doses. The FDA has said there is "serious" cardiovascular risks for patients who took "higher than recommended" doses of these drugs. Also, patients who don't respond well to initial anemia therapy (hyporesponders) are exposed to the highest heart risks.

These anemia drugs are approved to treat patients whose weakness and fatigue is caused by chronic kidney disease or by the side effects of cancer chemotherapy. They stimulate production of oxygen-carrying red blood cells, which can boost patients' energy and strength. The issue is over the drugs' safety on how big a dose to use to boost concentrations of hemoglobin. The FDA-approved level is doses sufficient to increase hemoglobin to a maximum of 12 grams a deciliter.

Blood transfusions are generally needed when patients slip to less than 8 grams. The adage of some physicians was that if some improvement in hemoglobin was good, higher levels of hemoglobin would even be better. However, clinical trials have shown the drugs can reduce the need for blood transfusions and improve the quality of life when used within the "original" dosing range.

New studies have raised questions whether these drugs might be harming patients. Those study results suggest the drugs may make the cancer worse. One such study published in the New England Journal of Medicine found that patients treated aggressively with Procrit had a higher risk of heart problems or death than those treated less aggressively.

As reported in OncoLink, patients and clinicians must understand that no data exists to support claims of improvement in quality of life or fatigue. The manufacturers of these agents frequently used direct consumer marketing to promote these unsupported claims, a fact that concerns many patient advocacy groups.

And now there is emerging evidence that pharmaceutical EPO can feed the growth of tumors in cancer patients (it IS a "growth factor" afterall).

A “growth factor” is about twenty small proteins that attach to specific receptors on the surface of stem cells in bone marrow and promote differentiation and maturation of these cells into morphotic constituents of blood. And blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). Problems with blood composition or circulation can lead to downstream tissue (which is made up of cells) dysfunction. If pharmaceutical EPO stimulates the bone marrow to make red blood cells, it could feed the growth of tumors in cancer patients.

The problem is that few drugs work the way oncologists think and few of them take the time to think through what it is they are using them for. Take medical oncologists out of the retail pharmacy business and force them to be cancer "doctors" again!

Source: Cell Function Analysis

[gdpawel]

The FDA backed CMS' National Coverage Decision (NCD), which limited use of the drugs because they have been shown to spur tumor growth.

The FDA has stated that the health risks associated with the use of pharmaceutical EPO (ESAs) for cancer patients include: Promotion of tumor growth in patients with advanced breast, head and neck, lymphoid, and non-small cell lung malignancies in studies adminstered EPO to target a hemoglobin of >12 g/dL, and have not been excluded with lower target hemoglobin levels.

The FDA believes that the approved labeling and CMS's National Coverage Decision are generally consistent in their recommendations regarding the use of pharmaceutical EPO in patients with cancer undergoing chemotherapy.

FDA's approved labeling recommends use of the lowest dose necessary to avoid the need for blood transfusions and transfusions are not normally given to patients whose hemoglobin is 10 g/dL or higher. The recommendation in the approved labeling that the hemoglobin not exceed 12 g/dL in cancer patients "is intended as an upper safety limit, not a target for therapy."

If ASCO has a complaint about CMS payment policy, it should provide evidence to the physicians at that agency who made the decision. There is no evidence that pharmaceutical EPO results in improved survival, "TUMOR CONTROL," health-related quality of life at any hemoglobin level in cancer patient undergoing chemotherapy.

Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. But companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment.

The anemia drugs are injected or given intravenously in physicians’ offices or dialysis centers. Doctors receive the rebates after they buy the drugs from the companies. But they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors’ purchase price.

It's still your mother's chemotherapy concession. Although the new Medicare bill tried to curtail the drug concession, private insurers still go along with it. What needs to be done is to remove the profit incentive from the choice of drug treatments. Let's take physicians out of the retail pharmacy business and force them to be doctors again!!!

http://www.house.gov/stark/news/110th/letters/20071012-esa.pdf

http://www.fda.gov/bbs/topics/NEWS/2007/NEW01582.html

http://www.nytimes.com/2007/05/09/business/09anemia.html?_r=3&hp=&oref=slogin&pagewanted=prin t&oref=slogin&oref=slogin

http://www.healthyskepticism.org/news/2007/Jun.php

[gdpawel]

EPO manufacturers and cancer societies have at least two lawmakers in their pocket in reference to anemia drugs. Representatives Anna Eshoo (D-Calif.) and Mike Rogers (R-Mich.) introduced legislation that would overturn a decision by the Centers for Medicare and Medicaid Services (CMS) to limit the circumstances under which Medicare will pay for anti-anemia treatments of cancer patients using pharmaceutical EPO. Legislation takes the form of a Congressional Review Act joint resolution, a rarely used tool that allows Congress to overturn regulatory decisions made by federal agencies.

The lawmakers allies in Congress, the American Society for Clinical Oncology, the American Society of Hematology and the cancer treatment center company US Oncology also are participating in the effort. The CMS policy affects the use of the drugs only for cancer patients, hence the fraternal organizations' involvement. The resolution is meant to serve as a reminder that special interests with a stake in Medicare coverage have friends in Congress.

Congress has been intensifying its scrutiny of Medicare spending on pharmaceutical EPO, which represents the single largest drug expense for the program. Some other key lawmakers view the manufacturers of EPO skeptically, citing Medicare's rising spending on the drugs. Earlier in the year, U.S. Oncology reported in their first quarter SEC Form 10-K report that cancer patients are suddenly using a lot less anemia drugs and as a result U.S. Oncology will bank $8-10 million a year less than expected.

CMS Wants More Proof Before Reconsidering ESA Decision

http://www.bioworld.com/servlet/com....&forceid=45568

Groups Ask Congress Not To Intervene In CMS Decision On Anemia Drugs

http://www.medicalnewstoday.com/articles/86023.php

[gdpawel]

The U.S. Food and Drug Administration approved revised boxed warnings and other safety-related product labeling changes for erythropoiesis-stimulating agents (ESAs), which treat certain types of anemia.

For patients with cancer, the new boxed warnings emphasize that ESAs caused tumor growth and shortened survival in patients with advanced breast, head and neck, lymphoid and non-small cell lung cancer when they received a dose that attempted to achieve a hemoglobin level of 12 grams per deciliter (g/dL) or greater.

The boxed warnings also emphasize that no clinical data are available to determine whether there is a similar risk of shortened survival or increased tumor growth for patients with cancer who receive an ESA dose that attempts to achieve a hemoglobin level of less than 12 g/dL. This is the hemoglobin level commonly achieved in clinical practice.

Health care providers determine whether a patient is anemic and decide on ESA dosing by measuring how much of the protein known as hemoglobin is present in a patient's red blood cells.

An earlier boxed warning, approved in March, described the results of six studies demonstrating that survival was shorter and tumors progressed faster when ESAs were used to achieve hemoglobin levels of 12 g/dL or greater in cancer patients.

Today's new boxed warning also clarifies that ESAs should only be used in patients with cancer when treating anemia specifically caused by chemotherapy and not for other causes of anemia. Moreover, it states that ESAs should be discontinued once the patient's chemotherapy course has been completed.

Health care professionals need to consider the risks of increased tumor progression and decreased survival in patients with cancer when prescribing ESAs. ESAs should be used in patients with cancer only when their anemia is due to chemotherapy and only at the lowest dose necessary to avoid the need for blood transfusions.

http://www.fda.gov/cder/drug/infopage/RHE/default.htm

[gdpawel]

Some cautionary information about being "overtreated" with anemia drugs. A study, published in the Canadian Medial Association Journal, suggests patients with anemia due to chronic disease are being dangerously overtreated. Anemia may actually help heal the body rather than harm it, says the new study.

Dr. Ryan Zarychanski, the study's co-author and a scientist at the Ottawa Health Research Institute, feels that doctors have been taught for generations that anemia is bad and they want to help their patients by treating it. However, they failed to consider that anemia may be adaptive and may be exactly the response that the body needs at that time.

Tired blood (anemia) involves a shortage of healthy red blood cells to carry oxygen to the body tissues. In the past, blood transfusions were the only way to treat anemia, until a drug derived from erythropoietin (EPO), a hormone that stimulates bone-marrow cells to produce red-blood cells.

Dr. Zarychanski pointed to evidence that suggests anemia is an evolutionary response to illness occuring in humans. The body has adapted over thousands of years to be anemic at times of stress because it needs to conserve energy. It needs help to fight infection. And when you're anemic, bacteria doesn't grow so well in the blood (an evolutionary response to infection before antibiotics).

In general, healthy adults have red blood cell levels of 14 grams or more per 100 millilitres of blood, while patients are considered to need treatment if their levels are below 10 grams. Patients with mild to moderate anemia (those with levels between 10 and 14 grams) would be better off not being treated.

What Dr. Zarychanski argues is that we should exercise some caution when thinking the best treatment is to automatically transfuse or give drugs to correct anemia.

Source: Ottawa Health Research Institute