Some Cancer Patients Benefit from Prophylactic Erythropoietin

WASHINGTON--Although the role of erythropoietin, or epoetin (Epogen, Procrit), in the treatment of chemotherapy-induced anemia is generally well known and accepted, its potential for prophylactic use to prevent the development of anemia in cancer patients remains at issue.

Nonetheless, recent research has provided a greater understanding of which cancer patients are likely to benefit from receiving erythropoietin before or during chemotherapy, Carole R. Chambers told the Sixth International Symposium on Oncology Pharmacy Practice (ISOPP).

"Patients at highest risk for transfusion are anemic prior to chemotherapy, and usually have lung cancer or leukemia," said Ms. Chambers, director of pharmacy, Alberta Cancer Board.

In Canada, research has indicated that the most likely candidates for early treatment with erythropoietin are patients who have symptomatic anemia affecting their functional capacity or quality of life; those who have a low baseline hemoglobin at the start of chemotherapy; and those who have a decline in their baseline, whatever the initial reading, of 20 g during chemotherapy.

"If one looks at the hemoglobin before the patient starts chemotherapy and again just before they get their second chemotherapy, and if it has dropped by 20 g, there is an 86% prediction of transfusion," Ms. Chambers said.

Abnormal Feedback Response

Anemia in cancer patients is characterized by shortened red blood cell survival, poor reutilization of iron, and an inadequate erythropoietin response. Normally, erythropoietin is released into the blood in response to low oxygen levels and stimulates an increased production of erythrocytes. "Cancer patients do not show the normal feedback response to increase their erythropoietin production," Ms. Chambers said.

The aim of erythropoietin therapy is to increase a patients’ quality of life and reduce the need for transfusion. However, some transfusions may still be necessary because it takes several days for injected erythropoietin to rev up the body’s response mechanism.

Oncology’s growing experience with erythropoietin has quieted some serious initial concerns. For example, no evidence of tolerance has emerged. And despite early fears that erythropoietin’s role as a growth factor might cause cancers to grow more rapidly, no such tumor stimulation has been shown, Ms. Chambers said.

"It is really important for patients to know that the early, significant side effects seen in the renal disease population (hypertension, seizures, thromboembolic events) have not been seen in the cancer population," she said.

Experience has also shortened the time needed to evaluate the effectiveness of erythropoietin in cancer patients and has offered guidance on when to stop such therapy. Until 1995, the rule was to evaluate after 8 weeks; now, evaluations more commonly take place at 4 weeks, and a few centers are trying to determine if a meaningful evaluation can be made in 2 weeks.

"If you haven’t gotten a response at 4 weeks, you may turn those nonresponders into responders by doubling their dose and evaluating them again in 4 weeks," Ms. Chambers said. "And if you still have not gotten a response, plan to discontinue the erythropoietin therapy. You are unlikely to get a response."

The issue of iron supplements continues to spark debate, with some experts arguing that virtually all anemic patients need additional iron. "But iron is not a great thing to tolerate as a patient," Ms. Chambers said. "I think the jury is still out on iron supplementation."

It is important that oncologists make clear to patients that while erythropoietin may improve their functional status and quality of life, it does not treat their underlying disease. "Thus," she said, "although they may feel better, this in no way indicates that their cancer is cured."

Ms. Chambers forecasts greater use of erythropoietin in a greater variety of cancers. And she predicts that very soon, important clinical questions will focus on which specific subsets of cancer patients will most benefit from erythropoietin therapy, in part because of the cost of the treatments. "Our challenge is to make sure we focus therapy on patients most likely to benefit and discontinue its use if they are not going to benefit," she concluded.