• 6/2/2008
  • web-based article
  • Amanda Gardner
  • U.S. News Health (health.usnews.com)

Widely prescribed blood-boosters might stimulate malignant cells, hasten death, study says.

Drugs used widely to treat anemia in cancer patients may actually speed progression of the cancer in certain individuals, but researchers report they may found a way to determine who those individuals are.

“We may have a test to predict whether a patient is susceptible to having their tumor progress if treated with erythropoietin and, alternatively, we may be able to predict patients it would be safe to treat with erythropoietin,” study author Dr. Tony Blau, of the University of Washington in Seattle, said during a Sunday news conference at the American Society of Clinical Oncology annual meeting in Chicago.

Recent controversy over erythropoiesis-stimulating agents (ESAs) such as Procrit, Epogen and Aranesp has centered around whether the blood-boosting drugs should be withdrawn from the market because of troubling side effects.

In March, a U.S. Food and Drug Administration advisory panel voted to recommend continued use of the drugs for patients on chemotherapy, unless the patient is likely to be cured. They also voted to recommend against the drugs’ use in patients with breast or head and neck cancer.

Eight clinical trials now suggest these medications actually speed the growth of tumors and shorten the lives of cancer victims.

The drugs’ manufacturers added a “black box” warning to the medications last November.

“There has been lots of controversy over these stimulating agents, and we have an FDA advisory committee to act on this as we speak,” said Dr. Julie Gralow, director of breast oncology at the University of Washington and Fred Hutchinson Cancer Center in Seattle and moderator of the Sunday news conference. “The drugs offer benefits in terms of reducing anemia and reducing transfusions, but several large trials in a variety of tumor types suggest that . . . these agents may have some stimulatory effects on tumor cells, faster progression in some cases, and more death in others.”

Until recently, Blau added, these drugs represented the biggest U.S. federal expenditures for oncology patients.

The results of the current study were based on analyses of tumor samples from 101 patients diagnosed with head and neck cancer who had participated in a previous phase III trial of erythropoietin.

Scientists measured levels of erythropoietin receptor (EpoR) messenger RNA (mRNA).

High levels of EpoR mRNA in patients who had undergone radiation but not surgery tended to signal a worse prognosis. There was a similar effect with Janus Kinase 2 (Jak2), the main intermediary of EpoR signaling, Blau added.

“These are preliminary findings, but they’re very exciting,” Gralow said. “If they hold up, they may mean that we may be able to use ESAs in targeted ways.”

“These findings must be considered preliminary until confirmed,” added Blau. “We believe that the definitive answer to this question lies locked in the filing cabinets of pathologists’ offices that contain tumors of patients who participated in already completed phase III studies.” That, of course, would be much easier than initiating entirely new studies.

A second study found the multiple drugs elderly cancer patients may already be taking could interact significantly with chemotherapy.

In particular, patients taking drugs that interfered with protein binding such as Norvasc for high blood pressure, Prilosec for heartburn, and the pain reliever Celebrex were more likely to experience hematologic side effects such as low white blood cell counts.

Patients taking drugs that act on a group of enzymes known as cytochrome p450 were more likely to experience effects such as fatigue or diarrhea. Examples of these drugs include the heart medications such as Pacerone and Cordarone.

“We found that all drugs patients are taking besides chemotherapy are likely to affect their tolerance to chemotherapy,” said study author Dr. Mihaela Popa, of the H. Lee Moffitt Cancer Center in Tampa, Fla.