A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer.
BACKGROUND
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.
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA. towonik@emory.edu
Taofeek K
TK
Owonikoko
Madhusmita
M
Behera
Zhengjia
Z
Chen
Chandar
C
Bhimani
Walter J
WJ
Curran
Fadlo R
FR
Khuri
Suresh S
SS
Ramalingam
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality; D015201:Meta-Analysis as Topic; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016879:Salvage Therapy; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate