T he best-selling oncology drugs in the United States, erythropoiesis-stimulating agents (ESAs), have been taken by about half of all U.S. cancer patients to treat chemotherapy-induced anemia — more than the number receiving radiation therapy. But that is changing. This summer, European and American regulatory authorities stringently restricted who should take ESAs, the most recent in a series of steps taken in response to clinical trials and basic research indicating that ESAs may harm cancer patients. Last year, the Centers for Medicare and Medicaid Services began denying coverage for the use of ESAs in cancer patients not undergoing chemotherapy and in those whose hemoglobin level is 10 g/dL or above. The center has further restricted use of darbepoetin, a second-generation, extendedrelease version, in patients undergoing chemotherapy. ESAs include epoetin alfa (Amgen’s Epogen and Procrit, which is manufactured by Amgen but licensed to Johnson & Johnson’s Ortho Biotech), Amgen’s longer-lasting darbepoetin alfa (Aranesp), and, in Europe, epoetin beta (NeoRecormon). The drugs are recombinant forms of erythropoietin (EPO), a naturally occurring hormone that is produced by the kidneys and controls red blood cell production. For the past 15 years, oncologists have prescribed ESAs to millions of anemic cancer patients in place of blood transfusions, hoping to improve their quality of life. Amgen scientists also reasoned that increasing anemic patients’ hemoglobin levels would help oxygenate tumors, thereby decreasing resistance to chemotherapy and radiation and improving outcomes. But a growing body of research on patients with head and neck, lymphoid, breast, cervical, and non – small-cell lung cancers and multiple myeloma indicates that patients taking ESAs have worse overall survival and tumor control when the drugs are given at hemoglobin levels higher than 12 g/dL. These patients are also more likely than patients who did not receive ESAs to have high blood pressure and thrombovascular events (TVEs). However, a study published in July in the Journal of Clinical Oncology suggested that patients with myelodysplastic syndrome treated long term with ESAs plus a white blood cell growth factor may have a survival advantage if they require few blood transfusions. But studies also show that ESAs reduce the need for transfusions only minimally, if at all, and that they usually do not imp rove patients’ quality of life. Ironically, the drugs were approved in 1993 as a safer alternative to blood transfusions just when the blood supply began to be screened for hepatitis B and C and human immunodeficiency virus, rendering blood much safer, while ESAs’ safety is now seriously questioned. The stakes in this controversy could hardly be higher: a large share of the profi ts of Amgen and Ortho Biotech; thousands of dollars of income for private practice oncologists who prescribe and administer these drugs; and, most important, the safety of cancer patients.
