title: Continuous versus intermittent chemotherapy strategies in metastatic colorectal cancer: a systematic review and meta-analysis.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors: Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Centre, Toronto scott.berry@sunnybrook.ca.
authors: S R
authors: SR
authors: Berry
authors: Department of Oncology, Program in Evidence-Based Care, McMaster University, Hamilton.
authors: R
authors: R
authors: Cosby
authors: Department of Oncology, Ottawa Hospital Cancer Centre, Ottawa.
authors: T
authors: T
authors: Asmis
authors: Division of Medical Oncology and Hematology, Sunnybrook Odette Cancer Centre, Toronto.
authors: K
authors: K
authors: Chan
authors: Queens University, Cancer Centre of Southeastern Ontario, Kingston.
authors: N
authors: N
authors: Hammad
authors: Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
authors: M K
authors: MK
authors: Krzyzanowska
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D000970:Antineoplastic Agents
keywords: continuous chemotherapy; intermittent chemotherapy; meta-analysis; metastatic colorectal cancer; systematic review