Gemcitabine Regimens Significantly Improve Advanced NSCLC

VANCOUVER, Canada-In ameta-analysis of 13 randomized trialsin patients with non-small-cell lungcancer (NSCLC), platinum-based regimenscontaining gemcitabine(Gemzar) offered a statistically significantimprovement in overall survivaland progression-free survival, comparedwith other platinum-based regimens.Joan Schiller, MD, professor ofmedicine, University of Wisconsin,Madison, presented the results at the10th World Conference on Lung Cancer(abstract O-239) on behalf of theinternational team of investigators."The gemcitabine-containing regimenswere clearly more effective thanolder regimens containing first- orsecond-generation chemotherapyagents, and at least as effective as thosewith other third-generation agents,"Dr. Schiller said.Guidelines issued in 1997 by theAmerican Society of Clinical Oncology(ASCO) recommended a platinumbasedregimen as optimal therapy inadvanced NSCLC. But there has beenno statistically significant survival benefitshown for any third-generationplatinum-based regimen, althoughgemcitabine/cisplatin (Platinol)showed a small advantage in terms oftime to progression in ECOG 1594,which compared four regimens, shenoted.Meta-Analysisof 13 TrialsThe study reported at the Vancouvermeeting was a meta-analysis of 13 trialsin which gemcitabine plus cisplatin orcarboplatin (Paraplatin) was comparedwith other platinum-based regimens inthe first-line treatment of stage IIIB/IVNSCLC. It was compiled through a comprehensivesearch of published andunpublished sources of all studies reportedby December 2002.A pooled hazard ratio was producedusing a fixed-effects meta-analysis. Statisticalheterogeneity was addressedwith a random-effects model when appropriate.An estimate of absolutetreatment benefit at 1 year was alsoconstructed.Dr. Schiller noted that heterogeneityof multiple studies constitutes apotential weakness of any meta-analysis,but she added that meta-analysisalso offers the strength of statisticalpower and the ability to generate aprecise estimate of treatment effect.This particular meta-analysis was ableto show advantages for gemcitabineplus a platinum agent that smaller studiescould not detect, she said.Thirteen eligible studies generateda pool of 4,556 patients in an analysisof 17 comparators: 12 against platinum-based doublets, including vinorelbine(Navelbine)/cisplatin (6),paclitaxel/cisplatin (2), paclitaxel/carboplatin(2), docetaxel (Taxotere)/cisplatin(1), and etoposide/cisplatin (1).Five studies included single-agent ortriplet-agent regimens, including mitomycin(Mutamycin)/cisplatin/vinorelbineor mitomycin/ifosfamide(Ifex)/cisplatin (4) and cisplatin (1).Benefit forGemcitabine ArmsFor overall survival, a slight butstatistically significant reduction inmortality in favor of the gemcitabinebasedarms was observed, with a hazardratio of 0.90. One-year survivalincreased from approximately 35% to39%, for an absolute survival differenceof 3.9% favoring gemcitabine.Two-year survival rose from 11.6% to14.2% with gemcitabine plus a platinum,Dr. Schiller reported.For progression-free survival aswell, there was a significant improvementreported with the gemcitabine -containing regimens, with a hazardratio of 0.87 and an absolute benefit at1 year of 4.2%.The same trend emerged in separateanalyses of older regimens andregimens containing third-generationagents. The hazard ratios were 0.89 foroverall survival and 0.85 for progression-free survival favoring gemcitabinearms vs older agents, and 0.93and 0.84, respectively, vs other thirdgenerationagents. "Altogether, six ofeight trials of newer agents favoredgemcitabine," Dr. Schiller said.The findings, she added, were upheldin a sensitivity analysis in whichall single or triplet comparator armswere excluded, with hazard ratios of0.92 for overall survival and 0.88 forprogression-free survival.