PHASE-I-II TRIAL OF ERYTHROPOIETIN IN THE TREATMENT OF CISPLATIN-ASSOCIATED ANEMIA

Background: Cancer patients undergoing chemotherapy with cisplatin-containing regimens often develop anemia. Although the cause is multifactorial, erythropoietin deficiency appears to play an important role. Recombinant human erythropoietin (epoetin) has been reported to be effective in reversing cisplatin-associated anemia in animal studies but not in clinical trials. Purpose: This phase I-II clinical trial was designed to assess the safety and efficacy of treatment with epoetin for anemia associated with cisplatin chemotherapy. Methods: Twenty-one cancer patients treated with cisplatin and manifesting anemia (hemoglobin level < 110 g/L) received epoetin at escalating doses (25, 50, 100, or 200 U/kg body weight) intravenously five times a week for 4 weeks. Results: Epoetin was well tolerated, and a maximal tolerated dose was not reached. Two patients experienced hypertension, which responded to standard antihypertensive therapy. No dose-dependent severe toxic effects were seen. The increase in hemoglobin levels from baseline on day 1 of the study was statistically significant after 4 weeks of epoetin therapy in the groups receiving 100 U/kg (mean change +/- SD = 19 +/- 13 g/L; P = .03) or 200 U/kg (mean change = 24 +/- 17 g/L; P = .007). A clinical response-an increase in hemoglobin level greater than 10 g/L-was achieved in 12 patients after 4 weeks of treatment. For these responders, the mean increase in hemoglobin level was 25 +/- 3.3 g/L over the level observed at the same time in the chemotherapy cycle preceding epoetin treatment, and this increase was statistically significant (P = .0001). Neither serum erythropoietin level nor hemoglobin level predicted a patient's response to epoetin. Conclusions: These preliminary findings suggest that epoetin is effective and well tolerated for the reversal of cisplatin-associated anemia, with the 100-U/kg and 200-U/kg dose levels offering optimal clinical response. Implications: We are conducting a phase III trial to determine the effect of epoetin on transfusion requirements in patients undergoing chemotherapy.