EFFECTS OF INTERLEUKIN-3 ON MYELOSUPPRESSION INDUCED BY CHEMOTHERAPY FOR OVARIAN-CANCER AND SMALL-CELL UNDIFFERENTIATED TUMORS

Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myclosuppre ssion. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 mug /kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatmen t differed. Constitutional symptoms were the major toxicity and in add ition to the carboplatin-induced nausea and vomiting the combination w as poorly tolerated. In 5115 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x), hy potension, severe malaise and bone pain. In this study, rhIL-3 amelior ated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhIL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferent iated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 mug/kg/ d). In this study, toxicity of the treatment was mild, however, no ben eficial haematologic effects of rhIL-3 could be demonstrated. In concl usion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatme nt (in relation to the expected nadir). In general rhIL-3-induced toxi city was mild, but combination with high dose carboplatin could be haz ardous if rhIL-3 is initiated at 24 h after the cytostatic agent.