Camptothecins Compared with Etoposide in Combination with Platinum Analog in Extensive Stage Small Cell Lung Cancer: Systematic Review with Meta-Analysis

Superiority of camptothecin regimens over etoposide—both combined with platinum analogs—in extensive disease small cell lung cancer has been a matter of debate with contradictory findings in randomized trials. A systematic review was sought to elucidate this issue. Randomized controlled trials compa...

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Published in:Journal of thoracic oncology 2010-12, Vol.5 (12), p.1986-1993
Main Authors: Lima, João Paulo S.N., Santos, Lucas Vieira dos, Sasse, Emma Chen, Lima, Carmen Silvia Passos, Sasse, André Deeke
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Camptothecin - administration & dosage
Cisplatin - administration & dosage
Disease-Free Survival
Drug therapy
Etoposide - administration & dosage
Humans
Lung neoplasms
Lung Neoplasms - drug therapy
Lung Neoplasms - mortality
Lung Neoplasms - pathology
Meta-analysis
Neoplasm Staging
Small Cell Lung Carcinoma - drug therapy
Small Cell Lung Carcinoma - mortality
Small Cell Lung Carcinoma - pathology
Small-cell lung carcinoma
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Summary:Superiority of camptothecin regimens over etoposide—both combined with platinum analogs—in extensive disease small cell lung cancer has been a matter of debate with contradictory findings in randomized trials. A systematic review was sought to elucidate this issue. Randomized controlled trials comparing first-line camptothecin-platinum doublets versus etoposide-platinum doublets in patients with extensive disease small cell lung cancer were searched in MEDLINE, EMBASE, LILACS, and CENTRAL databases, European Society of Medical Oncology, American Society of Clinical Oncology, and International Association for the Study of Lung Cancer meeting sites. Meta-analyses were performed using fixed-effects model. Subgroup analyses were undertaken comparing each type of camptothecin to etoposide-based regimens. The outcomes of interest were overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicities. Eight studies (3086 patients) were included. The meta-analysis of topotecan regimens (TP) was not reliable due to impending heterogeneity. Meta-analysis of trials testing irinotecan combinations (IP) versus etoposide regimens (EP; 1561 patients) stated an OS improvement in favor of IP arm, though with considerable heterogeneity, whose origin seemed to be a Japanese trial. In the analyses without that study (1407 patients left), IP brought a significant improvement in OS (hazard ratio = 0.87; 95% confidence interval 0.78–0.97; p = 0.02; I2 = 0). IP also increased PFS (hazard ratio = 0.83; 95% confidence interval 0.73–0.95; p = 0.006; I2 = 0%). There was no impact in RR (absolute RR 56% with IP; 53% with EP; p = 0.17). IP caused more diarrhea (p < 0.0001) but less hematological toxicities (p < 0.001) than EP. The present meta-analysis demonstrates statistically significant OS and PFS benefits of IP over EP regimens in western and eastern patients. Specific characteristics of safety profile should be taken into account when administrating IP chemotherapy.
ISSN:1556-0864
1556-1380
DOI:10.1097/JTO.0b013e3181f2451c