PHASE-I STUDY OF COMBINED ALPHA-INTERFERON, ALPHA-DIFLUOROMETHYLORNITHINE (DFMO), AND DOXORUBICIN IN ADVANCED MALIGNANCY

Interferon (IFN) and conventional cytotoxic chemotherapeutic agents ha ve been successfully combined in various studies. Alpha difluoromethyl ornithine (DFMO) is a novel antitumor agent which is an inhibitor of p olyamine metabolism. A phase I study of IFN 24 x 10(6) U/m(2)/day IM ( days 3-7), DFMO 9 gm/m(2) p.o. daily (days 1-7), and a variable dose o f doxorubicin starting at 20 mg/m(2) (day 6), of each 28 day cycle was performed. The aim of the study was to determine the maximally tolera ble dose of doxorubicin in this combination. Three patients were treat ed with doxorubicin at 20 mg/m(2) and six patients at 40 mg/m(2). The dose limiting toxicities were neutropenia, fatigue and fever. All othe r toxicities were mild and there was no grade TV toxicity. A doxorubic in dose of 40 mg/m(2) produced tolerable toxicity and is recommended f or phase II studies. No major antitumor effects were seen.