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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / mortality
  • Meta-Analysis as Topic
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Salvage Therapy*
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / mortality*
  • Survival Rate