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Phase I Trial of Escalating Dose Doxorubicin Administered Concurrently with ₂-Interferon¹

Division of Oncology, Department of Medicine, The Rita and Stanley Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016

The clinical use of ₂-interferon and doxorubicin is based on in vitro and preclinical in vivo observations of synergistic antitumor efficacy. To test this combination a Phase I clinical and pharmacokinetic study of the concurrent use of ₂-interferon and doxorubicin was initiated in patients with malignant solid tumors. Each 5-wk treatment cycle consisted of 3 wk of drug administration and 2 wk of rest. The ₂-interferon was administered s.c. at a constant dose of 10 million IU/m² on Mondays, Wednesdays, and Fridays in all patients while the doxorubicin was administered weekly beginning with a dose of 5 mg/m² and escalated to the maximum tolerated dose of 25 mg/m². At least three evaluable patients were entered at each dose level, and no dose escalations were allowed within patients. The dose-limiting toxicities were granulocytopenia and thrombocytopenia. Hepatic enzyme elevations and systemic symptoms due to interferon occurred at all dose levels. None was severe or dose limiting, and all were reversible. These toxicity data suggest that the hepatotoxic effects of interferon do not enhance doxorubicin toxicity when given by this dose and schedule. Doxorubicin plasma levels were measured at each dose level. The recommended dose of doxorubicin is 25 mg/m² per wk when administered with 10 million IU/m² of interferon in this schedule. This schedule allows for the administration of a greater total dose of doxorubicin than has been achieved when given every 3 wk with the same dose and schedule of ₂-interferon in a parallel study.

¹ Supported by a grant from the Schering Corporation.

Received 11/17/86. Revised 4/27/87. Revised 10/27/87. Accepted 12/17/87.