This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and <or=2 adverse prognostic factors. Patients were randomised to receive six cycles of either ACE (doxorubicin 50 mg/m(2) i.v., cyclophosphamide 1 g/m(2) i.v. and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) or PE (cisplatin 80 mg/m(2) and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) given for every 3 weeks. For patients where cisplatin was not suitable, carboplatin (AUC6) was substituted. A total of 280 patients were included (139 ACE, 141 PE). The response rates were 72% for ACE and 77% for PE. One-year survival rates were 34 and 38% (P=0.497), respectively and 2-year survival was the same (12%) for both arms. For LD patients, the median survival was 10.9 months for ACE and 12.6 months for PE (P=0.51); for ED patients median survival was 8.3 months and 7.5 months, respectively. More grades 3 and 4 neutropenia (90 vs 57%, P<0.005) and grades 3 and 4 infections (73 vs 29%, P<0.005) occurred with ACE, resulting in more days of hospitalisation and greater i.v. antibiotic use. ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD, and should not be studied further in this group of patients.