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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

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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.

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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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Authors and Affiliations

  1. Department of Oncology, The Sixth People’s Hospital, Shanghai Jiao Tong University, No. 600, Yishan Road, Shanghai, 200233, China

    Wei-Xiang Qi, Li-na Tang, Ai-na He, Zan Shen, Feng Lin & Yang Yao

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  1. Wei-Xiang Qi
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  2. Li-na Tang
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  3. Ai-na He
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  4. Zan Shen
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Correspondence to Yang Yao.

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Qi, WX., Tang, Ln., He, An. et al. 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. Lung 190, 477–485 (2012). https://doi.org/10.1007/s00408-012-9399-3

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  • DOI: https://doi.org/10.1007/s00408-012-9399-3

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