more concerns about drugs stimulating rbc production

[AlaskaAngel]

http://www.reuters.com/article/healt...28933220070223

[AlaskaAngel]

http://www.fda.gov/medWatch/SAFETY/2...05.htm#aranesp

Aranesp (darbepoetin alfa)
Audience: Oncologists, hematologists and other healthcare professionals
FDA and Amgen notified healthcare professionals of revisions to the WARNINGS and PRECAUTIONS sections of the prescribing information for Aranesp, indicated for the treatment of chemotherapy-induced anemia in patients with nonmyeloid malignancies. This safety information alerts physicians to the adverse effects observed with other products in this class in association with off-label dosing strategies. Two recent investigational studies with other erythropoietic products permitted or required dosing to achieve hemoglobin levels of greater than 12 grams per deciliter. An increased frequency of adverse patient outcomes, including increased mortality and thrombotic vascular events were reported in these studies. As indicated in the Aranesp prescribing information, the target hemoglobin level should not exceed 12 grams per deciliter in men or women.

[AlaskaAngel]

Not immediately recent, but more detailed info to consider:

http://www.sciencedaily.com/upi/inde...n-analysis.xml

[AlaskaAngel]

After accessing, scroll down for info on anemia drugs:

http://www.accessdata.fda.gov/script...pt.cfm?show=63

[gdpawel]

EPO is a "natural" substance made by the kidney. It stimulates the bone marrow to make red blood cells. Healthy adults are usually at about 15 grams a deciliter. For cancer patients, upping the production of "natural" EPO via our hair follicles could be very beneficial.

Increasing the hemoglobin level above 12 is very risky with "pharmaceutical" EPO. Pharmaceutical EPO makes sludgy blood. When normal people take it, their blood gets too thick and they die of heart attacks and strokes.

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 take "higher than recommended" doses of these drugs.

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, if red blood cells are brought back to "normal" levels.

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.

The adage of some physicians is 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.

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.

As Dr. Weissmann stated, "the study also is important because it suggests that there is still much to learn about well known processes in the body." 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!

[gdpawel]

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