Phase I-II study of high-dose epirubicin in advanced non-small-cell lung cancer.

PURPOSE: A phase I multicenter trial was performed to determine the maximum-tolerated dose (MTD) of epirubicin, given on 3 consecutive days every 3 weeks to previously untreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: After appropriate staging and a baseline multiple-gated angiogram (MUGA) scan, at least four patients were entered at each dose level, starting at 35 mg/m2 of epirubicin given intravenously (IV) daily for 3 days (105 mg/m2) and escalating by 5 mg/m2 per injection in each dose level (15 mg/m2 per course). Epirubicin was administered up to a maximum dose of 60 mg/m2/d for 3 days (180 mg/m2). The MTD was determined to be 55 mg/m2/d for 3 days (165 mg/m2) after treating a total of 35 (33 assessable) patients. Nadir granulocyte counts and associated febrile episodes comprised the dose-limiting toxicity, but there were no treatment-related deaths. A phase II trial was performed using a dose of 50 mg/m2/d for 3 days (150 mg/m2) every 3 weeks with no dose escalation, but with dose reduction for toxicity as required. A total of 30 patients were entered onto this phase of the study. RESULTS: The major toxicity, as in the phase I trial, was neutropenia with five febrile episodes, again with no treatment-related deaths. An overall response rate of 12 of 63 (19%) was noted in the combined patient population of the phase I-II trial, with 95% confidence intervals of 10% to 31%. When the response rate was analyzed by histology, only one of 17 (6%) patients with squamous histology, as compared with 11 of 46 (24%) with non-squamous histology, responded, but this did not reach statistical significance (P = .15). CONCLUSIONS: High-dose epirubicin is tolerable and is an active single agent in NSCLC. It should be combined with relatively nonmyelosuppressive agents such as cisplatin to try to obtain higher response rates and extend the survival in this disease.