AbstractIn an attempt to address the schedule of adjuvant chemotherapy in surgically resected T1 or T2NOMO small cell lung cancer, 12 patients were randomized to receive 6 courses of either single-agent (high-dose epirubicin) or combination (cyclophosphamide, epirubicin, and etoposide) chemotherapy, at 3-week intervals. No thoracic radiotherapy was administered while prophylactic cranial irradiation (30 Gy/10 fractions/2 weeks) was given. With a 25-month median followup, overall estimated 2-year and median survival were 83% and 26.5 months (range 16–34+), respectively. Ten patients are currently alive and disease free. No significant difference in 2-year survival was observed between the two adjuvant treatment modalities and median survival was 28 months (range 13–34+) for combination and 21 months (range 14–29+) for single-agent chemotherapy. Although at high doses, epirubicin resulted in a moderate clinical and histological cardiotoxicity and a remarkably reduced incidence of severe (WHO grades 3 and 4) treatment-related morbidity compared with the combination regimen. These preliminary results suggest that comparable survival and reduced toxicity might be expected with an active single-agent as adjuvant chemotherapy in TI or T2NOMO small cell lung cancer.