VANCOUVER, Canada-In a meta-analysis of 13 randomized trials in patients with non-small-cell lung cancer (NSCLC), platinum-based regimens containing gemcitabine(Drug information on gemcitabine) (Gemzar) offered a statistically significant improvement in overall survival and progression-free survival, compared with other platinum-based regimens. Joan Schiller, MD, professor of medicine, University of Wisconsin, Madison, presented the results at the 10th World Conference on Lung Cancer (abstract O-239) on behalf of the international team of investigators. "The gemcitabine-containing regimens were clearly more effective than older regimens containing first- or second-generation chemotherapy agents, and at least as effective as those with other third-generation agents," Dr. Schiller said. Guidelines issued in 1997 by the American Society of Clinical Oncology (ASCO) recommended a platinumbased regimen as optimal therapy in advanced NSCLC. But there has been no statistically significant survival benefit shown for any third-generation platinum-based regimen, although gemcitabine/cisplatin (Platinol) showed a small advantage in terms of time to progression in ECOG 1594, which compared four regimens, she noted. Meta-Analysis of 13 Trials The study reported at the Vancouver meeting was a meta-analysis of 13 trials in which gemcitabine plus cisplatin or carboplatin(Drug information on carboplatin) (Paraplatin) was compared with other platinum-based regimens in the first-line treatment of stage IIIB/IV NSCLC. It was compiled through a comprehensive search of published and unpublished sources of all studies reported by December 2002. A pooled hazard ratio was produced using a fixed-effects meta-analysis. Statistical heterogeneity was addressed with a random-effects model when appropriate. An estimate of absolute treatment benefit at 1 year was also constructed. Dr. Schiller noted that heterogeneity of multiple studies constitutes a potential weakness of any meta-analysis, but she added that meta-analysis also offers the strength of statistical power and the ability to generate a precise estimate of treatment effect. This particular meta-analysis was able to show advantages for gemcitabine plus a platinum agent that smaller studies could not detect, she said. Thirteen eligible studies generated a pool of 4,556 patients in an analysis of 17 comparators: 12 against platinum- based doublets, including vinorelbine (Navelbine)/cisplatin (6), paclitaxel(Drug information on paclitaxel)/cisplatin (2), paclitaxel/carboplatin (2), docetaxel(Drug information on docetaxel) (Taxotere)/cisplatin (1), and etoposide(Drug information on etoposide)/cisplatin (1). Five studies included single-agent or triplet-agent regimens, including mitomycin(Drug information on mitomycin) (Mutamycin)/cisplatin/vinorelbine or mitomycin/ifosfamide (Ifex)/cisplatin (4) and cisplatin(Drug information on cisplatin) (1). Benefit for Gemcitabine Arms For overall survival, a slight but statistically significant reduction in mortality in favor of the gemcitabinebased arms was observed, with a hazard ratio of 0.90. One-year survival increased from approximately 35% to 39%, for an absolute survival difference of 3.9% favoring gemcitabine. Two-year survival rose from 11.6% to 14.2% with gemcitabine plus a platinum, Dr. Schiller reported. For progression-free survival as well, there was a significant improvement reported with the gemcitabine - containing regimens, with a hazard ratio of 0.87 and an absolute benefit at 1 year of 4.2%. The same trend emerged in separate analyses of older regimens and regimens containing third-generation agents. The hazard ratios were 0.89 for overall survival and 0.85 for progression- free survival favoring gemcitabine arms vs older agents, and 0.93 and 0.84, respectively, vs other thirdgeneration agents. "Altogether, six of eight trials of newer agents favored gemcitabine," Dr. Schiller said. The findings, she added, were upheld in a sensitivity analysis in which all single or triplet comparator arms were excluded, with hazard ratios of 0.92 for overall survival and 0.88 for progression-free survival.