EFFECTS OF INTERLEUKIN-1-ALPHA ON CARBOPLATIN-INDUCED THROMBOCYTOPENIA IN PATIENTS WITH RECURRENT OVARIAN-CANCER

Purpose: The purpose of this study was to evaluate the clinical safety and ability of interleukin-1α (IL-1α) to ameliorate carboplatin-induced thrombocytopenia and thus allow patients with ovarian cancer to receive multiple cycles of chemotherapy at full doses. Patients and Methods: IL-1α was administered by continuous intravenous infusion daily at doses of 0.1 to 10 μg/m2/24 hours over 4 days (96 hours) before the first cycle and/or following the second cycle of carboplatin in 21 patients with recurrent ovarian cancer who had platinum-responsive disease. In cycle no. 1, patients received carboplatin (400 mg/m2) alone, while in cycle no. 2 carboplatin was followed by IL-1α. Results: Treatment with IL-1α before carboplatin was associated with moderate leukocytosis (baseline mean, 6.15 x 103/μL; maximum mean, 17.9 x 103/μL; P < .001) and significant increases in platelet counts (baseline mean, 241 x 103/μL; maximal mean, 392 x 103/μL; P < .001). IL-1α following carboplatin significantly reduced the duration of thrombocytopenia (days platelet count < 50,000, 5.1 to 2.9 days; P = .003) and increased the area under the curve (AUC) of platelets as a function of time (P < .001). The mean nadir platelet counts were 54,000/μL and 67,000/μL (P = .08) in cycles no. 1 and 2, respectively. In fact, seven of 12 patients given 3 μg/m2/d of IL-1α had less thrombocytopenia in cycle no. 2 than in cycle no. 1. Treatment with IL-1α was associated with the tolerance of multiple cycles of carboplatin at the same dose in several patients. The maximum-tolerated dose (MTD) was 3 μg/m2/d; fever, chills, hypotension, and fluid retention were dose-limiting toxic effects. Conclusion: These findings demonstrate that IL-1α can enhance recovery of platelets following carboplatin therapy and suggest a potential therapeutic role for IL-1α in attenuating thrombocytopenia associated with chemotherapy.