A phase III randomised trial testing chemotherapy in extensive small-cell lung cancer (SCLC)

In a meta-analysis of the literature (Lung Cancer 30: 23-36; 2000), we showed survival benefits for regimens including cisplatin (Hazard ratio HR 0.61; 95 % CI, 0.57–0.66) and for those including etoposide (HR 0.65; 0.61–0.69).That benefit was mainly observed in favour of regimens including etoposide alone or in combination with cisplatin, justifying the use of each of these drugs. In order to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide, extensive-SCLC patients were randomised between cisplatin-etoposide (CE) and ifosfamide-etoposide-epirubicin (IVE) between 2000 and 2013. 176 and 170 eligible patients were respectively allocated to CE and IVE (315 events – deaths – were required before analysis according to the statistical considerations). Patients were well balanced for age, sex, performance status (PS), stage, neutrophil count. Best objective response rates were not significantly different: 60 % with CE and 59 % with IVE. Progression-free survival was similar. There was also no significant difference in survival with median time, 1-year and 2-year rates respectively of 9.6 months, 31 % and 5 % for CE and 10 months, 39 % and 9 % for IVE. HR was 0.84 (95 % CI 0.68-1.05), p=0.16 (ref = CE). When adjusted for prognostic factors (sex, PS, weight loss, neutrophil count), HR was 0.83 (95% CI, 0.65-1.08), p=0.17. In term of toxicity, CE was associated with more thrombopenia and IVE with more leucopenia. Early death by toxicity was documented in 18 and 10 patients respectively. In conclusion, combination of cisplatin and etoposide failed to improve survival in comparison to an etoposide-containing regimen without cisplatin.