Phase I Trial of Escalating dose Doxorubicin Administered Concurrently with α2-interferon

Michael David Green, James Leonard Speyer, Howard S. Hochster, Leonard F. Liebes, Susan Dunleavy, Tova Widman, James Carter Wernz, Ronald Howard Blum, Robert Jay Spiegel, Franco Mario Muggia

Research output: Contribution to journalArticlepeer-review


The clinical use of α2-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 a2-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 α2-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 α2-interferon in a parallel study.

Original languageEnglish
Pages (from-to)2574-2578
Number of pages5
JournalCancer Research
Issue number9
StatePublished - May 1988
Externally publishedYes


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