Early Intervention With Epoetin Prevents Anemia in NSCLC Patients

VANCOUVER, Canada- Recombinant human erythropoietin(Drug information on erythropoietin) (epoetin alfa, Epogen, Procrit) administered to patients with non-small-cell lung cancer (NSCLC) who are undergoing chemotherapy has been found to significantly reduce the incidence of anemia, compared with best supportive care, and to improve quality of life. Robert Milroy, MD, of Stobhill General Hospital, Glasgow, United Kingdom, presented the study findings at the 10th World Conference on Lung Cancer (abstract O-253). "The biggest reduction in quality of life occurs when Hb drops from 12 to 11 g/dL," Dr. Milroy said. "We wanted to see if it is possible to prevent anemia in patients by early intervention with epoetin alfa(Drug information on epoetin alfa) [to possibly] improve quality of life and even survival." The international, phase III study randomized 380 patients with stage IIIb (48%) or stage IV (51%) (1% unspecified) NSCLC who were receiving cisplatin(Drug information on cisplatin) (Platinol)-based or carboplatin(Drug information on carboplatin) (Paraplatin)-based chemotherapy. Eligibility criteria included hemoglobin of 15 g/dL or less for men and 14 g/dL or less for women. Patients were randomized on a 1:1 basis to receive 10,000 IU epoetin alfa subcutaneously three times weekly or best supportive care, which included chemotherapy. Treatment with epoetin alfa was initiated when hemoglobin dropped below 13 g/dL in men and below 12 g/dL in women. Patients whose hemoglobin levels were at 13 g/dL (men) and 12 g/dL (women) at study entry (the immediate treatment group) received epoetin alfa immediately. Other patients started chemotherapy and began epoetin alfa when their hemoglobin dropped below the trigger points (the delayed treatment group). Epoetin alfa was administered for up to 4 weeks following the last cycle of chemotherapy. The study duration was 28 weeks. The mean hemoglobin level at study baseline was 12.7 g/dL (range 7.7 to 15.3 g/dL). Quality of life was assessed with the FACT-An (Functional Assessment of Cancer Therapy- Anemia) subscale. Study Results Results show that overall, 8.9% of patients treated with epoetin alfa required blood transfusions, compared with 24.3% of those receiving best supportive care (P < .0001). This represents a transfusion reduction of more than 50%. There was also a significant difference between the active treatment and best-supportive-care groups with respect to stabilized hemoglobin. In the entire study population, patients treated with epoetin alfa had stabilized hemoglobin at greater than 12.5 g/dL throughout the study period, whereas patients in the best-supportive-care group experienced a steady decline (P < .001). A subgroup analysis of the immediate and delayed epoetin alfa treatment groups showed that the strategy of early use did work, "particularly the early treatment in patients with low hemoglobin at the outset," Dr. Milroy said. Immediate epoetin alfa treatment maintained hemoglobin levels during chemotherapy, despite significantly fewer blood transfusions (P < .001), he said. Data on the delayed-treatment group showed a fall in hemoglobin initially, followed by stabilization. "The point is that in the treated patients, epoetin alfa was able to maintain hemoglobin of between 12.5 and 12.7 g/dL. In the best-supportive-care control arm, the patients became significantly anemic," Dr. Milroy said. "The strategy to prevent anemia worked." Quality of Life Immediate epoetin alfa intervention, but not delayed treatment, reduced the decline in quality of life. "This may be because the delayed group had started with normal hemoglobin and then drifted down by over a gram before they could start epoetin alfa," Dr. Milroy said. The most striking survival finding, he said, was that the patients in the immediate- treatment group, who were anemic at the study outset, had much worse survival regardless of epoetin alfa treatment, compared with patients in the delayed treatment group. The results show a highly statistically significant difference between the immediate and delayed treatment groups' survival of 24.8% and 48.1%, respectively (P < .0001). "We all know hemoglobin is an individual prognostic factor, but this is a striking change," Dr. Milroy said. "We didn't see any benefits from epoetin alfa either in the immediate or the delayed arms in terms of survival benefits. We were disappointed by that." However, the data showed a 20% improvement in overall survival among patients with baseline hemoglobin of 13 g/dL or more (male) and 12 g/dL or more (female), compared with patients who had lower baseline hemoglobin. "The strategy works; epoetin alfa was able to keep patients' hemoglobin levels up and prevent anemia, and that was consistent for both the immediate and delayed treatment groups," Dr. Milroy said.