RANDOMIZED TRIAL OF RECOMBINANT HUMAN INTERLEUKIN-3 VERSUS PLACEBO INPREVENTION OF BONE-MARROW DEPRESSION DURING FIRST-LINE CHEMOTHERAPY FOR OVARIAN-CARCINOMA

Purpose: To determine whether recombinant human interleukin-3 (rhIL-3) reduces bone marrow depression and improves chemotherapeutic schedule adherence in ovarian cancer patients receiving first-line combination chemotherapy. Patients and Methods: In a randomized multicenter study , 185 patients received carboplatin (dose based on projected area unde r the concentration-time curve [AUC] = 4) and cyclophosphamide (750 mg /m(2)) day 1, every 3 weeks for six cycles. Patients were randomized t o receive rhIL-3 (5 mu g/kg) or placebo once daily subcutaneously on d ays 3 to 12. Results: Adherence to chemotherapeutic regimen, mean chem otherapy cycle length, tumor response rate, and median survival at 24 months did not differ between groups. The number of side effects-prima rily allergic reactions, flu-like symptoms and fever-were higher in th e rhIL-3 group, which resulted in 21 discontinuations compared with on e in the placebo group. Compared with placebo, the rhIL-3 group had hi gher patients with World Health Organization (WHO) grade IV thrombocyt openia or number of platelet transfusions did not differ. Leukocyte co unts differed only in cycles 1 and 2 between groups, The leukocyte nad ir occurred earlier in the rhIL-3 (day 12) than in the placebo group ( day 15, P = .006). Leukocytes and neutrophils were only higher in the rhIL-3 group day 1 of cycle 2. In cycles 4 and 5, more patients with W HO grade IV neutropenia received rhIL-3 (P < .005). Eosinophil counts were higher day 1 of cycles 2 to 6 in the rhIL-3 group (P < .0001). Co nclusion: rhIL-3 had stimulatory hematopoietic effects. This did not r esult either in reduction of platelet transfusions or in improvement o f chemotherapeutic schedule adherence. There were more side effects in the rhIL-3 group than in the placebo group. rhIL-3 at 5 mu g/kg/d is, therefore, not of clinical benefit in this chemotherapeutic regimen. (C) 1998 by American Society of Clinical Oncology.