First Published Online May 7, 2009 The Oncologist, Vol. 14, No. 5, 497-510, May 2009; doi:10.1634/theoncologist.2008-0260 © 2009 AlphaMed Press
Impact of Third-Generation Drugs on the Activity of First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analytical ApproachaMedical Oncology A, Disease Management Team - Lung Cancer, National Institute for Cancer Research, Genova, Italy; bDepartment of Medical Oncology, University Hospital of Udine, Piazzale S. M. della Misericordia, Udine, Italy; cDepartment of Medical Oncology, Mirano Hospital, Via L. Mariutto, Mirano, VE, Italy Key Words. Non-small-cell lung carcinoma • Meta-analysis • Gemcitabine • Docetaxel • Paclitaxel • Vinorelbine Correspondence: Francesco Grossi, M.D., Medical Oncology A, Disease Management Team - Lung Cancer, National Institute for Cancer Research, Largo R. Benzi, 10, 16132 Genova, Italy. Telephone: 39-010-560-06-65 (office) or 39-335-525-54-84 (mobile); Fax: 39-010-560-08-50; e-mail: francesco.grossi{at}istge.it Received December 1, 2008; accepted for publication March 24, 2009; first published online in THE ONCOLOGIST Express on May 7, 2009.
Disclosures: Francesco Grossi: Honoraria: Eli Lilly, Sanofi-Aventis, Roche; Marianna Aita: None; Carlotta Defferrari: None; Francesco Rosetti: None; Annalisa Brianti: None; Gianpiero Fasola: Honoraria: Roche, Eli Lilly, Sanofi-Aventis; Orazio Vinante: None; Paolo Pronzato: None; Giovanni Pappagallo: Honoraria: Eli Lilly, Sanofi-Aventis.
Background. The therapeutic equivalence of different third-generation agents in the first-line treatment of advanced non-small cell lung cancer (NSCLC) has long been accepted, although recent studies seem to suggest some superiority of gemcitabine- or docetaxel-containing regimens over other third-generation doublets.
Objective. To assess the relative impact of different third-generation drugs on the activity of first-line chemotherapy in advanced non-small cell lung cancer by considering both response and progressive disease (PD) rates as outcome measures.
Methods. Published and unpublished data were collected from randomized trials comparing a gemcitabine-, docetaxel-, vinorelbine- or paclitaxel-containing regimen with one or more gemcitabine-, docetaxel-, vinorelbine- or paclitaxel-free combinations. For each study, 2 x 2 tables were constructed for both response and immediate progression. Pooled odds ratios were calculated using a general variance-based method.
Results Forty-five trials (11,867 patients) were eligible. The odds of obtaining an objective response to treatment were similar across different regimens. Gemcitabine-based chemotherapy was associated with a 14% lower risk for immediate progression, whereas patients receiving paclitaxel showed a 22% higher risk for having PD as the best response. Docetaxel treatment provided a nonsignificant 9% lower odds for progression.
Conclusions. These data demonstrate that different third-generation regimens have comparable activity in chemotherapy-naïve patients with advanced NSCLC. Gemcitabine-based chemotherapy provides better disease control, whereas the risk for immediate progression is significantly higher when paclitaxel-containing regimens are used.
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