The progression-free survival (PFS) of cyclophosphamide/doxorubicin/etoposide (CDE) and carboplatin/paclitaxel (CP) was compared in chemonaive patients with extensive disease small-cell lung cancer (ED-SCLC). A total of 203 patients were randomised to three-weekly CDE (n=102) or CP (n=101) for five cycles. Tumour response rates in CDE and CP were 60% and 61%. PFS of CP was 5.2 months, PFS of CDE 4.9 months (p=0.60). The major difference in toxicity between CDE and CP was grade 4 leukocytopaenia in 64% and 9% of the patients (p<0.0001), leading to febrile neutropaenia in 30% and 4% of the patients (p<0.0001), respectively. This was the reason for differences in the total number of hospital admissions (63 for CDE and 40 for CP, p=0.0025). This study failed to demonstrate any benefit in PFS with CP compared with CDE. CP was associated with significantly less haematological toxicity, leading to 37% less hospital admissions for febrile neutropaenia.