Thrombocytopenia induced by high-dose chemotherapy remains a significant clinical problem that limits dose intensification of many chemotherapy agents. In our phase I trial of IL-1alpha, we noted increased megakaryocytes in the bone marrow and an increase in the platelet count after IL-1alpha treatment. We designed the present trial to determine if IL-1alpha could ameliorate the thrombocytopenia induced by chemotherapy. We chose carboplatin to combine with IL-1alpha because it has considerable antitumor activity, but is limited by bone marrow suppression, especially thrombocytopenia. This study has enrolled 72 patients to date. Fifty- five patients have receive IL-1alpha by IV bolus: twelve patients were in a control group and received carboplatin alone (8 mg/m2); five patients each received IL-1alpha before carboplatin at 0.03, 0.1 and 0.3 microgram/kg; five patients received 0.03 microgram/kg IL-1alpha after carboplatin and 11 patients each received 0.1 IL-1alpha after carboplatin and 10 patients received 0.3 microgram/kg IL-1alpha after carboplatin. Seventeen patients have received IL-1alpha by subcutaneous injection, before or after carboplatin. Toxicities observed in this trial were similar to those observed with previous trials of either agent alone. IL- 1alpha treatment after carboplatin significantly accelerated platelet recovery and shortened the duration of sever thrombocytopenia at the 0.3 microgram/kg IL-1alpha dose. Treatment with IL-1alpha before high dose carboplatin had no effect. Five of 15 patients at the two highest IL- alpha doses given after carboplatin ha minimal thrombocytopenia. IL-1alpha treatment produced dose related increases in the serum level of IL-6 and G-CSF. Subcutaneous IL-1 administration after carboplatin has similar platelet supportive effects as intravenous IL-1 without causing hypotension or other severe toxicities. IL-1 given subcutaneously is well-tolerated as an out-patient regimen. This trial provides conclusive evidence that IL-1alpha treatment can significantly ameliorate chemotherapy induced thrombocytopenia.
