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. 2012 May;7(5):866-72.
doi: 10.1097/JTO.0b013e31824c7f4b.

A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer

Taofeek K Owonikoko  1 , Madhusmita Behera, Zhengjia Chen, Chandar Bhimani, Walter J Curran, Fadlo R Khuri, Suresh S Ramalingam
Affiliations

A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer

Taofeek K Owonikoko et al. J Thorac Oncol. 2012 May.

Abstract

Introduction: Small-cell lung cancer (SCLC) patients unresponsive or relapsing within 90 days after frontline chemotherapy have poor prognosis and are treated with regimens different from the first-line regimen. Potential differences in the efficacy of second-line therapy for refractory and sensitive SCLC have not been well studied.

Methods: Studies that enrolled sensitive and refractory (relapse < 90 days or > 90 days) SCLC patients for second-line therapy were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library), and meeting abstracts databases. A systematic analysis was conducted using Comprehensive Meta Analysis (version 2.2.048) software to calculate the odds ratio of response and 95% confidence interval. Median overall survival time for sensitive and resistant SCLC patients was compared by two-sided Student's t test. We tested for significant heterogeneity by Cochran's chi-square test and I-square index.

Results: Twenty-one studies published between 1984 and 2011 were eligible for this analysis with a total of 1692 patients enrolled; 912 with sensitive and 780 with refractory SCLC. The overall response rate was 17.9% with a higher response rate of 27.7% (range, 0%-77%) for sensitive SCLC versus 14.8% (range, 0%-70%) for refractory patients; p=0.0001. Pooled overall odds ratio of response was 2.235 (95% confidence interval: 1.518-3.291; p=0.001) favoring patients with sensitive disease. Median overall survival time was 6.7 months with a weighted survival of 7.7 and 5.4 months for sensitive and refractory SCLC, respectively (p = 0.0035).

Conclusions: Refractory SCLC patients derive modest clinical benefit from second-line chemotherapy. However, response and survival outcomes are superior with chemosensitive disease.

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Figures

Figure 1
Figure 1
Consort diagram detailing search strategy and study selection for this systematic analysis
Figure 2
Figure 2
Forest plot showing the primary analysis using a random effect model for Odds ratio of response to salvage chemotherapy between patients with sensitive disease or refractory SCLC as defined based on response to frontline chemotherapy
Figure 3
Figure 3
Forest plot of analysis using a fixed effect model for Odds ratio of response to salvage chemotherapy between patients with sensitive disease or refractory SCLC as defined based on response to frontline chemotherapy.
Figure 4
Figure 4
Forest plot showing the result of Odds ratio analysis after excluding large studies that enrolled 50 or more patients
Figure 5
Figure 5
Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated topotecan
Figure 6
Figure 6
Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated combination multi-agent therapy
Figure 7
Figure 7
Forest plot of the result of systematic analysis for Odds ratio of response to salvage chemotherapy after excluding studies that evaluated single agent treatment regimens
See this image and copyright information in PMC

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