title: The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a systematic review and practice guideline.
abstract: BACKGROUND
  This clinical practice guideline, based on a systematic review, was developed to determine which chemotherapeutic agents (or combinations of agents) show the highest response rates, improved survival, quality of life, or symptom control in patients with advanced malignant pleural mesothelioma.
  
  
  METHODS
  A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials, published as articles and abstracts, were selected and assessed. External feedback was obtained from Ontario clinicians, and the guideline was approved by the provincial Lung Cancer Disease Site Group.
  
  
  RESULTS
  One hundred nineteen studies were eligible, including eight randomized trials and 111 phase II trials. The pooled response rates from phase II trials suggest that response rates with combination chemotherapy are higher than with single agents. Data from the largest randomized controlled trial demonstrated that chemotherapy with cisplatin and pemetrexed significantly improves response rates (41% versus 17%, p < 0.001), time to progression (5.7 months versus 3.9 months, p = 0.001), and overall survival (median, 12.1 months versus 9.3 months, hazard ratio = 0.77, p = 0.020) in comparison to single-agent cisplatin. A second trial demonstrated cisplatin and raltitrexed significantly improved median survival compared to single-agent cisplatin (11.4 months versus 8.8 months; hazard ratio = 0.76, p = 0.0483). Overall response rate (24% versus 14%, p = 0.056) was greater in the combination treatment arm, but this difference was not statistically significant.
  
  
  CONCLUSIONS
  There is good evidence to recommend chemotherapy with pemetrexed and cisplatin for adult patients with symptomatic advanced malignant pleural mesothelioma. Such treatment should be administered with supplementation of vitamin B12 and folic acid. If pemetrexed is not available, cisplatin plus raltitrexed is a reasonable alternative.
authors.affiliation: McMaster University at Hamilton Health Sciences and Juravinski Cancer Centre, Hamilton, Ontario, Canada. vanderja@mcmaster.ca
authors.forename: Peter
authors.initials: P
authors.lastname: Ellis
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: William K
authors.initials: WK
authors.lastname: Evans
authors.forename: Adam E
authors.initials: AE
authors.lastname: Haynes
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Lloyd
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D018579:Patient Selection; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D011799:Quinazolines; D013876:Thiophenes; D000068437:Pemetrexed; D006147:Guanine; C068874:raltitrexed; D002945:Cisplatin