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. Al-though the cause is multifactorial, erythropoietin deficiency appears to play an important role. recombinant human erythropoietin (epoetin)has been trported to be effective in reversing cisplatin-associated anemia in animal studies but not in clinical trials. Purpose: This phase I-II clinical trial with epotin for anemia associted with cisplatin chemo therapy. Methods: Twenty-one cancer partients treated with cisplatin and manifesting anemia (hemogolbin level < 110 g/ L) received eopetin at escalating dose (25, 50, 100, Or 200 U/ kg boby weight) intravenously five tomes a week for 4 weeks. Results: Epoetin was well tolerated, and a maximal tolerated dose was not reached. Two patients experienced hypertension, which reponded to strandard antihypertensive therapy. No dose-dependent severe toxic effects were seen. The increase in hemoglobin levels from baseline on day 1 or the stuy was statistically significant after 4 weeks of eopetin therapy in the groups receiving 100 U/ kg; (mean change=±17 g/ L; p=. 007). A clinical reponse — an increase in hwmoglobin level grater than 10 g/ l was achieved in 12 patients after 4 weeks of treatment. For these responder, the mean increase in hemoglobin level was 25 ± 3.3 g/ L over the level nor hemoglobin level predicated 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 optiaml clinical reponse. Implications: We are conducting a phase III trial to determine the effect of epoetin on transfusion requirements in patients undergoing chemotherapy. [j Nati cancer inst 84: 98–103,1992]