A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis

Purpose: Cisplatin (CDDP) and etoposide (VP16) are considered major standar d cytotoxic drugs for small cell lung cancer (SCLC). The present systematic review had as its objective the evaluation of their role, as components of chemotherapy regimens, on survival. Methods: Published randomised clinical trials (from 1980 to 1998) were selected comparing, in SCLC patients, chem otherapy regimens, given as first-line therapy. One arm (the experimental a rm) had to include CDDP and/or VP16, while another had to omit the same dru g(s). Trials quality was assessed by two published scores (Chalmers and Eur opean Lung Cancer Working Party (ELCWP)). For each individual trial. the ha zard ratio (HR) of the survival distributions was estimated on the basis of reported statistics or, if not available, by extracting, from the survival graphical representations, the data required to construct the difference b etween expected and observed numbers of events as calculated in the log-ran k statistic. A combined hazard ratio was obtained by the Peto method (a val ue <1 meaning a benefit for CDDP and/or VP16). Results: Thirty-six trials e ligible for our systematic review were identified, classified into four gro ups (I-IV): group I, I trial testing a CDDP-based regimen (without VP16) ag ainst another arm not including either CDDP or VP16; group II, 17 trials te sting a VP16-based regimen (without CDDP) against a regimen without VP16 an d CDDP; group III, nine trials comparing a regimen including CDDP and VP16 with a regimen using neither drug; and, finally, group IV, nine trials comp aring a regimen based on both drugs with a regimen based on VP16 only. Over all, Chalmers and ELCWP scores correlated well (r(S) = 0.76, P < 0.001) and had respective median scores of 50.3 and 63.7%. The number of eligible pat ients did not have a significant impact on the scores as well as the trials group, the trial positivity (a positive trial defined as showing itself a statistically significant survival benefit for the experimental regimen), o verall or in categories, and the year of publication. Combined hazard ratio s with 95% confidence intervals were: 0.70 (0.41-1.21) for group I, 0.72 (0 .67-0.78) for II, 0.57 (0.51-0.64) for III, and 0.74 (0.66-0.83) for IV, sh owing a survival benefit in favour of regimens including etoposide alone or in combination with cisplatin, justifying with high significance levels th e use of each of these drugs. Overall survival benefits could also be shown for regimens including CDDP (HR = 0.61; confidence interval (CI), 0.57-0.6 6), as well as for those including VP16 (HR = 0.65; CI, 0.61-0.69). Robustn ess of these results has to be confirmed with appropriate randomised trials , (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.