A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis
Introduction
Polychemotherapy has been a main progress in the curative treatment of small cell lung cancer (SCLC). The first used regimens included cyclophosphamide (CPA), methotrexate, vincristine (VCR) and/or lomustine (CCNU). In the 1970s, a new combination was developed, called VAC and containing VCR, adriamycine (ADR) and CPA. Later, etoposide (VP16) and cisplatin (CDDP) were shown to be major active agents and their combination (EP) is today considered by most authors as the standard induction chemotherapy regimen for SCLC [1]. However, the randomised studies testing these drugs have given contradictory results, preventing, up to now, recommendation of the cisplatin–etoposide regimen with a high level of evidence.
The purpose of the present study was to assess the role of CDDP and VP16 in the medical treatment of SCLC by performing a systematic review of the randomised trials published in the literature with a qualitative evaluation of their methodology and an aggregation (meta-analysis) of the survival results.
Section snippets
Materials and methods
Criteria for eligibility of a trial to the present systematic review were the following: to deal only with small cell lung cancer, to be randomised, to have been published as a full paper between 1980 and 1998 in two major languages and one minor language, as those languages were those understandable by all the readers (English and French, and Dutch), to include at least 15 eligible patients per arm, and to compare first-line chemotherapy regimens, with an experimental arm containing CDDP
Results
Thirty-six studies, corresponding to a total of 40 publications [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49] and of 7173 randomised patients, were selected. Their main characteristics are shown in Table 1. The median number of eligible patients per study was 153 (range, 59–577). Ten trials dealt with
Discussion
This systematic review, by pooling all randomised trials comparing chemotherapy regimens with or without etoposide and/or cisplatin, revealed a positive effect on survival of the administration of these drugs in small cell lung cancer. As shown by the meta-analysis, in each of the four groups (Table 4), survival improvement is achieved by the use of regimens with etoposide but without cisplatin or of regimens with both drugs. It was not possible to analyse the role of cisplatin in regimens
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