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Lung

, Volume 190, Issue 5, pp 477–485 | Cite as

Doublet Versus Single Cytotoxic Agent as First-Line Treatment for Elderly Patients with Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

  • Wei-Xiang Qi
  • Li-na Tang
  • Ai-na He
  • Zan Shen
  • Feng Lin
  • Yang YaoEmail author
Article

Abstract

Background

The aim of this study was to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy of doublet versus single third-generation cytotoxic agent as first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC).

Methods

Several databases including PubMed, Embase, and Cochrane databases were searched. The endpoints were overall survival (OS), time to progression (TTP), 1-year survival rate (1-year SR), overall response rate (ORR), and grade 3 or 4 adverse event (AE). We performed a meta-analysis of the randomized controlled trials using a fixed-effects model and an additional random-effects model when applicable. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). A subgroup meta-analysis was performed based on chemotherapy regimens.

Results

Ten eligible trials involving 2,510 patients were identified. The intention-to-treatment (ITT) analysis demonstrated that doublet therapy was superior to single agent in terms of OS (HR = 0.84, 95 % CI = 0.71–1.00, p = 0.053), TTP (HR = 0.76, 95 % CI = 0.60–0.96, p = 0.022), 1-year SR (RR = 1.17, 95 % CI = 1.02–1.35, p = 0.03), and ORR (RR = 1.54, 95 % CI = 1.36–1.73, p = 0.000). Subgroup analysis also favored platinum-based doublet therapy in terms of 1-year SR (RR = 1.40, 95 % CI = 1.09–1.81, p = 0.009) and ORR (RR = 1.64, 95 % CI = 1.38–1.96, p = 0.000). Though gemcitabine-based doublet significantly increased ORR compared with single agent (RR = 1.45, 95 % CI = 1.23–1.71, p = 0.000), it did not translate into an increase in survival benefits. In addition, more incidences of grade 3 or 4 anemia, thrombocytopenia, and neurotoxicity were observed in the doublet combination group. With respect to grade 3 or 4 neutropenia and nonhematologic toxicities such as diarrhea, fatigue, nausea, and vomiting, equivalent frequencies were found between the two groups.

Conclusions

Our results indicated that doublet therapy was superior to a single third-generation cytotoxic agent for elderly patients with advanced NSCLC. The optimal dosage and schedule of platinum-based doublet should be investigated in future prospective clinical trials. Gemcitabine-based doublet could be considered for elderly patients who were not suitable for platinum-based chemotherapy.

Keywords

Non-small-cell lung cancer Elderly Doublet Single agent First-line treatment 

Notes

Acknowledgments

The study was supported by grants from the National Natural Science Foundation of China (81001191) and Science and Technology Commission of Shanghai (10PJ1408300).

Conflict of interest

Wei-Xiang Qi, Li-na Tang, Zan Shen, Ai-na He, Feng Lin, and Yao Yang have no conflicts of interest to disclose.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Wei-Xiang Qi
    • 1
  • Li-na Tang
    • 1
  • Ai-na He
    • 1
  • Zan Shen
    • 1
  • Feng Lin
    • 1
  • Yang Yao
    • 1
    Email author
  1. 1.Department of OncologyThe Sixth People’s Hospital, Shanghai Jiao Tong UniversityShanghaiChina

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