F.D.A. Warning Is Issued On Anemia Drugs' Overuse

[gpawelski]

The New York Times article states that the drugs, given by injection, have been heavily advertised, and there is evidence that they have been overused, in part because oncologists can make money by using more of the drug.

http://query.nytimes.com/gst/fullpage.h ... A9619C8B63

According to Dr. John Glaspy, director of UCLA's Outpatient Oncology Clinic, one complicating factor, experts say, is that oncologists make significant revenue buying cancer drugs from manufacturers and charging patients a higher price for receiving the drugs in their offices. That profit motive could influence some doctors' decisions. However, patients with anemia, which can cause sluggishness in its early stages and can be fatal in advanced phases, can get blood transfusions, typically every few weeks, instead of using EPO.

Len Lichtenfeld, deputy chief medical officer for the Atlanta-based American Cancer Society, told United Press International, "Probably more than a billion dollars is spent on erythropoietin each year, which makes it one of the most expensive cancer drugs." A six-month course of treatment can cost more than $10,000 per patient.

In panel discussion that highlighted the 12th annual conference of the National Comprehensive Cancer Network, Lee Newcomer, former chief medical officer and currently an executive with Minneapolis-based United Health Group, pointed out that in reviewing records of patients who were prescribed the drug erythropoietin, said that 44% of those patients had blood work-ups that would indicate they were not anemic.

http://www.sciencedaily.com/upi/index.p ... alysis.xml

U.S. Oncology takes a hit! Reports first-quarter net loss.

U.S. Oncology said a number of factors impacted the results, including reduced pre-tax income due to lower use of certain supportive care drugs used to treat cancer-induced anemia: and the discontinuation of the Medicare Demonstration Project.

http://www.bizjournals.com/houston/stor ... from_rss=1

The Senate Finance Committee Chairman found that the value of the approximately $300 million-a-year Medicare Demonstration Project to report on a patient's level of nausea, vomiting, pain and fatigue was for nothing.

CMS paid chemotherapy providers $130 per report, per infusional-chemotherapy recipient, on a patient's level of nausea, vomiting, pain and fatigue. However, HHS' inspector general's office found these providers were being paid an extra $130 to simply forward the data that was already collected.

A continuance of the Medicare Demonstration Project would have exacerbated existing economic and clinical problems instead of resolving them by increasing the temptations for physicians to overuse injectable drugs and promise to aggravate the ecnomic problems Congress attempted to fix with the new Medicare law.

U.S. Oncology Under the Gun

U.S. Oncology reports two seeming unrelated bits in their latest SEC Form 10-K. One note say 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. The second note says that in 2005 the company was subpoenaed by the U.S. Department of Justice about contracts and relationships with pharmaceutical companies.

Coincidence?

http://www.prnewswire.com/cgi-bin/stori ... 9964&EDATE

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 drug 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 let them be doctors again!!!

[gpawelski]

New studies have raised questions whether these drugs might actually be harming them. Those study results suggest the drugs may make the cancer worse.

Dr. Eric Winer, director of the breast oncology center at Dana-Farber Cancer Institute feels that these drugs are presumed to be entirely safe, given for supportive care and to improve quality of life, but not actually used to treat cancer. But the drugs may have been used in ways not approved on the labels.

A study published in the New England Journal of Medicine last November found that patients treated aggressively with Procrit had a higher risk of heart problems or death than those treated less aggressively.

Amgen, the maker of Aranesp, announced late January that in one of its clinical trials, patients were more likely to die than those getting a placebo. The trial was testing the drug in patients whose anemia was caused by the cancer itself, not by chemotherapy. While a Danish study in patients with head and neck cancer had to be stopped early because the cancer seemed to recur more in patients being treated with Aranesp.

In February, the Journal of Clinical Oncology published a paper describing a small Canadian trial in lung cancer patients had also been stopped early because those getting Eprex were dying sooner. While Roche suspended patient enrollment in a lung cancer trial comparing its Cera against Amgen's Aranesp because of greater than expected number of deaths in at least some of the arms of the trial.

It is not known why the drugs may cause these problems. It is known that raising hemoglobin levels too high increases the risk of blood clots. While most of these trials did aim to increase hemoglobin above the levels recommended in the drugs' labels, that was not the case with Amgen's own trial.

There is some evidence that clots were not the problem in the trials, but that Epo may spur tumor growth. Some studies suggest that certain tumor cells, such as those in head and neck cancer, have proteins on their surface that bind to Epo. When that happens, it sets off a cascade of reactions spurring growth.

Studies done by Dr. Jennifer R. Grandis, professor at the University of Pittsburgh, found enough biologic possibility that they can serve as a growth factor for the cancer cell.

Concerns about the safety of the drugs for cancer were first raised in 2003 by two studies that showed patients getting Epo had worse outcomes. Until then, these drugs had shown signs that they could improve the quality of life for cancer patients, even though their safety labeling has already been revised three times since 1997.

Whiz bang therapies often get a pass on toxicities because they are just so darn cool. The problem is that few drugs work the way we think and few physicians/scientists take the time to think through what it is they are using them for.

Source: TherapeuticsDaily

[stand4hope]

I don't know for sure what all this means, or if any of it's true. All I know is my husband's oncologist can become the richest man in the world and I will gladly cheer him on and add to his pot of money, as long as he continues to strive to keep my husband alive - WHICH HE DOES!!!!!!!!!!!!!!

Peggy

[gpawelski]

What needs to be done is to remove the profit incentive from the choice of cancer treatments. Patients should receive what is best for them and not what is best for their oncologists. What it means is that we need to aim higher.

[karenl]

---

[teresag]

I'm skeptical about Public Interest Watch. Their website gives precious little information about who they are, how they choose their causes, who comprises their board of directors, and what their sources of funding are. All I could find under the "About Us" link was

Initial funding for PIW has been provided by business organizations.

What business organizations would that be? They do not say.

They condemn the American Heart Association for allowing Subway to use its logo, saying "The American Heart Association has no business selling its endorsement to fast-food companies.....There is simply no way to justify this type of conduct by a non-profit that relies on taxpayers to finance its operations."

This statement is misleading, suggesting that AHA is a federal agency that relies on taxes for its support. AHA is largely financed by contributions and fundraising events. Also, on the AHA website, anyone can download and read the annual report. They practice full disclosure; PIW does not.

So I'd suggest taking PIW's claims with a big grain of salt.

Incidentally, oral chemotherapy is not covered by Medicare, so there is a disincentive built into the reimbursement system for use of oral agents. This is fueled by the huge cost of oral chemotherapy to the patient. Ask anyone here who's on Iressa. Cost of 30 250 mg tablets Iressa at http://www.drugstore.com: $1,719.92 - 90 tablets is $5,079.51.

This is the real crime.

[gpawelski]

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

[gpawelski]

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/l ... 12-esa.pdf

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

http://www.nytimes.com/2007/05/09/busin ... ref=slogin

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

[karenl]

Thanks, Greg.

As always, very interesting.

Karen

[gpawelski]

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.acc ... ceid=45568

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

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

[gpawelski]

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

[gpawelski]

The FDA received new data on risks of anemia drugs, which is consistent with previous data on tumor growth and death. Two more studies provide further evidence of the risks of anemia drugs. The studies show that patients with breast or advanced cervical cancers who received EPO drugs to treat anemia caused by chemotherapy died sooner or had more rapid tumor growth than similar patients who didn't receive the anemia drug. The two studies were not among the six studies that were described in revised labeling approved by the FDA November 8, 2007.

http://www.fda.gov:80/bbs/topics/NEWS/2 ... 01769.html

Gee, could it be that increased numbers of red cells deliver more oxygen to the tumor cells and thereby increase their activity across the board, including with respect to invasion, proliferation, and metatstasis? On one hand we're developing drugs to halt and reverse angiogenesis while on the other hand we're helping the tumor to obtain more oxygen with existing vasculature. And nobody in charge foresaw that? Amazing how they can apply differing standards for proof or benefit when profit is involved.

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. 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.