THE EFFECTS OF TREATMENT WITH INTERLEUKIN-1-ALPHA ON PLATELET RECOVERY AFTER HIGH-DOSE CARBOPLATIN

Background. Thrombocytopenia is a frequent side effect of cancer chemotherapy and commonly limits attempts to escalate drug doses. To determine whether interleukin-1alpha could ameliorate carboplatin-induced thrombocytopenia, we combined it with high-dose carboplatin in 43 patients with advanced neoplasms. Methods. High-dose carboplatin (800 mg per square meter of body-surface area) was administered alone to a control group. Subsequent patients were randomly assigned to receive the same dose of carboplatin with interleukin-1alpha, administered either before or after carboplatin. Interleukin-1alpha was given intravenously at a dose of 0.03, 0.1, or 0.3 mug per kilogram of body weight per day for five days. Results. Carboplatin alone consistently produced thrombocytopenia with a median nadir of 19,000 platelets per cubic millimeter and a median of 10 days with less than 1 00,000 platelets per cubic millimeter. All 15 patients receiving interleukin-1alpha before carboplatin had similar findings. In contrast, 5 of the 15 patients given one of the two higher doses of interleukin-1alpha after carboplatin had minimal thrombocytopenia (nadir, 91,000 to 332,000 platelets per cubic millimeter). In the 10 patients given 0.3 mug of interleukin-1alpha per kilogram after carboplatin treatment, the platelet count recovered to 100,000 per cubic millimeter significantly earlier than in either the control group (P = 0.002) or the patients who received interleukin-1alpha before carboplatin (P = 0.003), with the median times to recovery in the three groups being 16, 21, and 23 days, respectively. At the highest dose of interleukin-1alpha, toxicity was substantial (but reversible), requiring inpatient support for hypotension, supraventricular arrhythmias, and pulmonary-capillary leak. Conclusions. Interleukin-1alpha can accelerate the recovery of platelets after high-dose carboplatin therapy and may be clinically useful in preventing or treating thrombocytopenia induced by chemotherapy.