Effects of interleukin-1 alpha on carboplatin-induced thrombocytopenia in patients with recurrent ovarian cancer

Abstract

Purpose: The purpose of this study was to evaluate the clinical safety and ability of interleukin-1 alpha (IL-1 alpha) 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-1 alpha was administered by continuous intravenous infusion daily at doses of 0.1 to 10 micrograms/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-1 alpha.

Results: Treatment with IL-1 alpha before carboplatin was associated with moderate leukocytosis (baseline mean, 6.15 x 10(3)/microL; maximum mean, 17.9 x 10(3)/microL; P < .001) and significant increases in platelet counts (baseline mean, 241 x 10(3)/microL; maximal mean, 392 x 10(3)/microL; P < .001). IL-1 alpha 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/microL and 67,000/microL (P = .08) in cycles no. 1 and 2, respectively. In fact, seven of 12 patients given 3 micrograms/m2/d of IL-1 alpha had less thrombocytopenia in cycle no. 2 than in cycle no. 1. Treatment with IL-1 alpha was associated with the tolerance of multiple cycles of carboplatin at the same dose in several patients. The maximum-tolerated dose (MTD) was 3 micrograms/m2/d; fever, chills, hypotension, and fluid retention were dose-limiting toxic effects.

Conclusion: These findings demonstrate that IL-1 alpha can enhance recovery of platelets following carboplatin therapy and suggest a potential therapeutic role for IL-1 alpha in attenuating thrombocytopenia associated with chemotherapy.