Phase II feasibility study of high dose epirubicin-based regimens for untreated patients with small-cell lung cancer.

17 previously untreated patients with small cell lung cancer entered a phase II study testing the feasibility of incorporating high dose epirubicin (110 mg/m2, day 1) in combination regimens, including cyclophosphamide (1 g/m2, day 1), and etoposide (120 mg/m2, day 1) (courses 1, 3, 5) or cisplatin (60 mg/m2, day 1) and etoposide (120 mg/m2, days 1-4) (courses 2, 4, 6), every 3 weeks. Complete responders with limited or extensive disease received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. All patients were evaluable for toxicity and response. Myelosuppression and stomatitis were the dose-limiting side-effects. Maximum myelosuppression occurred as granulocytopenia and anemia, but a recovery by day 21 was observed in the majority of courses. Neutropenic fever occurred in 47 of 99 courses. Severe stomatitis was experienced in 25 courses and lasted generally 7-12 days. Acute cardiac toxicity was uncommon and represented by mild to moderate rhythm abnormalities. No change was noted in the mean QRS voltage on electrocardiogram (ECG) and no patient had a decline of greater than or equal to 20% in the cardiac ejection fraction and/or episode of overt heart failure at any stage of treatment. The overall objective response rate was 88%, with six (35%) complete and nine (53%) partial responses. With a median follow-up of 16 months, overall median survival was 13 months (range, 2-18+). This study demonstrates that epirubicin, at the present dose and schedule, is feasible in combination regimens and that cardiotoxicity is not dose-limiting and induced or enhanced by thoracic irradiation and/or cyclophosphamide.