PHARMACOKINETIC REEVALUATION AND PHASE-I STUDY OF HIGH-DOSE EPIRUBICIN IN ADVANCED NONSMALL CELL LUNG-CANCER

We performed a phase I trial to evaluate the toxicity and the maximum tolerated dose of high dose epirubicin on a three-consecutive-day sche dule on Japanese patients with advanced non-small cell lung cancer. Fo urteen patients were entered in the study. At least three patients wer e assigned to each different dose level. Epirubicin was given intraven ously daily for three day by bolus injection. The dose was started at 60 mg/m2/course and escalated by 30 mg/m2/course. Granulocytopenia was found to be the dose limiting toxicity with a maximum tolerated dose of 150 mg/m2/course. Thrombocytopenia and non-hematological toxicities were mild and well tolerated. The maximum tolerated dose was lower th an that in Europe and Canada. Partial responses were observed in two o ut of five patients on 150 mg/M2/Course. The recommended phase 11 dose for high dose epirubicin was demonstrated to be 120 mg/m2/Course. A f urther dose-escalating study of epirubicin in conjunction with the adm inistration of granulocyte colony stimulating factor is scheduled for the determination of its antitumor activity in non-small cell lung can cer.