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Cumulative meta-analysis of randomized trials comparing gemcitabine-based chemotherapy versus gemcitabine alone in patients with advanced or metastatic pancreatic cancer (PC)

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: E. Banu, S. Oudard, A. Banu, A. Fodor, B. Landi, T. Lecomte, P. Laurent-Puig, P. H. Cugnenc, J. M. Andrieu

Editorial: Poster presentation. Abstract 4101. J Clin Oncol (supplement) 2005;23(16S):333s., 2005.


Background: Most individual trials have been to small to show clear benefit of gemcitabine (GEM) combination therapy comparing to GEM alone. Previously published meta-analysis exploring this hypothesis (Fung, ASCO 2003) included 1503 patients in 7 studies and failed to demonstrate any additional benefit of GEM combination on overall survival (OS). Methods: The end points were the effect on OS of GEM-based combination comparing to GEM alone in pts with advanced or metastatic PC and the relationship between GEM intended dose-intensity (DI) and OS. Randomized controlled trials (RTC) were included if they provided an OS assessment with presentation of the survival graph and time-to-event data. The number of pts at risk and deaths were extracted from survival curves and adjusted based on the extent of follow-up. Pooled relative risk reduction (RRR) with 95% confidence interval (CI) at 6, 12 and 18 months were calculated using a fixed effects model (EasyMa software). Heterogeneity was analyzed using Cochran method. Results: The meta-analysis was performed on an intention to treat basis. Results were based on published data of 3314 pts (1649 pts treated with GEM combinations and 1665 pts with GEM alone) included in 14 RCT. GEM was combined with platinum salt (43%), 5-FU derivates (29%) and others (28%).The follow-up range was 2.9–71.8 months. No differences of age, sex, performance status and stage of disease were found among studies. We found an OS benefit at all time points for pts treated with GEM combination [RRR of 9% (CI 3–16%), 4% (CI 0–7%) and 3% (CI 0–6%) at 6, 12 and 18 months, respectively]. Subgroup analyses suggested a benefit for pts included in RCT that tested the same planned DI of GEM in two arms at all time points and for platinum salt association (only at 6 and 18 months). Heterogeneity and rank test for publication bias were not statistically significant. Conclusions: The available evidence suggest that GEM combination therapy improves OS compared to GEM alone. Ongoing, prospectively RCT will help better define the efficacy of these new combinations and will determine if they result in a significant benefit when compared to GEM monotherapy.

Cuvinte cheie: cancer de pancreas avansat, chimioterapie, supravietuire, meta-analiza // advanced pancreatic cancer, chemotherapy, meta-analysis, survival