Phase I trial of interleukin-2 plus doxorubicin

Interleukin-2 (IL-2) and doxorubicin have synergistic antitumor activity in selected animal models and may interact favorably in the therapy of human tumors. In order to explore the interactions between these agents and to define a maximum tolerated dosage for the combination, we performed a phase I clinical trial of IL-2 administered by continuous intravenous infusion (c.i.) plus doxorubicin given by intravenous bolus. Fifteen patients were treated on one of two schedules; the first seven patients received IL-2, 9 mIU/m2/day (3 patients) or 13.5 mIU/m2/day (4 patients) by c.i. on days 1-5, 8-12, and 15-19 with doxorubicin, 25 mg/m2 on day 14. Eight patients received IL-2, 18 mIU/m2/day by c.i. on days 1-5 and 8-12 with doxorubicin, 25 mg/m2 (4 patients) or 50 mg/m2 (4 patients) on day 7. The toxicities of the combination were no greater than those expected from each agent individually. Patients at all three planned IL-2 dosage levels received similar percentages of the planned total dosage (median 100%; > 95% in 60% of cycles), and all patients received the planned dosages of doxorubicin with only one brief delay for resolution of hyperbilirubinemia. The doses recommended for further study are IL-2, 18 mIU/m2/day, on days 1-5 and 8-12 with doxorubicin, 50 mg/m2 on day 7, a regimen which is not associated with significant organ toxicity.