Abstract
ABSTRACT Background The impact of the duration of chemotherapy on the outcomes of patients with advanced colorectal cancer is controversial. Our objective was to perform a systematic review and meta-analysis of randomized controlled trials (RCT) that compared chemotherapy continuously administered until disease progression versus chemotherapy interruption in patients with metastatic colorectal cancer. Methods We systematically searched for all RCT in which metastatic colorectal cancer patients were randomized to continuous therapy until progression or chemotherapy discontinuation after maximal response or fixed number of cycles. Trials were located through searches of PubMed, Cochrane Library and of ASCO/ESMO abstracts up to February 2012. Two authors independently extracted the data, and consensus was achieved when there was disagreement. Meta-analyses were performed using random-effects model. Hazard ratios (HR) were used for the meta-analysis and were expressed with 95% confidence intervals (CI). Statistical heterogeneity of data was evaluated with the chi-square test, and expressed using the I2 index. Results Our search retrieved 42 RCT, of which five were eligible, with 1815 patients included. The analysis of progression-free survival (PFS) was not possible due to the different definitions of PFS across trials. The median chemotherapy free interval in the discontinuation group was 3.9 months. The pooled analysis of overall survival included 1776 patients (one trial was not included because it did not present extractable data). The metanalysis showed a statistically significant survival benefit with continuously given chemotherapy (HR = 0.90, 95% CI = 0.82 to 0.99; p = 0.03; I2 0%) in comparison to chemotherapy holiday strategy. Quality of life was reported in one trial and no difference was found in it. Conclusions Chemotherapy delivered continuously until tumor progression appears to be associated with a modest but significantly better survival in patients with advanced colorectal cancer over chemotherapy interruption. Continued therapy may be available for selected patients with more aggressive disease. Disclosure All authors have declared no conflicts of interest.
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