Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: a systematic review and meta-analysis

Background: An important goal of intermittent strategies of delivering systemic treatment as first-line treatment of metastatic colorectal cancer (mCRC) is to maintain efficacy while improving patients' quality of life (QoL). Given the varying impact on efficacy demonstrated in individual randomized, controlled trials (RCTs), a systematic review and meta-analysis of RCTs of these intermittent strategies was carried out.

Design: Relevant databases were systematically searched for the period 2000-2014. RCTs that compared a continuous versus intermittent strategy of delivering systemic treatment were identified by a systematic review. Overall survival (OS) hazard ratios (HRs) were extracted from the most recently reported trial results. The results of identified trials were clinically homogeneous so the data were pooled using Review Manager software (RevMan 5.1).

Results: Eleven RCTs were identified (n = 4 854). For the eight (n = 4508) trials with available HRs, the treatment patients received after induction was: none (five trials, n = 3036), fluoropyrimidine (one trial, n = 620), and biologic (two trials, n = 852). There were no statistically significant survival differences observed between the continuous and intermittent chemotherapy strategies. There was no statistically significant difference observed between continuous and intermittent strategies [HR = 1.03, 95% confidence interval (CI) 0.96-1.10, P = 0.38)]. Subgroup analyses demonstrated results were generally robust across induction and maintenance regimens. One subgroup analysis of the three trials (CAIRO3, OPTIMOX2, COIN, n = 2403) with combination treatment induction and no maintenance until progression revealed a statistically, but nonclinically significant benefit for continuous treatment (HR = 1.10, 95% CI 1.00-1.20, P = 0.049). QoL life was either the same in both arms in two trials (n = 912) or improved in the intermittent strategy arm in one trial (n = 1630).

Conclusion: Intermittent strategies of delivering systemic treatment of mCRC do not result in a clinically significant reduction in OS compared with a continuous strategy of delivery, and should be part of an informed discussion of treatment options with patients with mCRC.