title: Third-line chemotherapy in small-cell lung cancer: an international analysis.
abstract: BACKGROUND
  Small-cell lung cancer is an aggressive disease for which the mainstay of treatment is chemotherapy. Despite good initial responses most patients will relapse. Some will receive second-line therapy with clinical benefit, but for third-line chemotherapy there is little evidence to guide treatment decisions and the benefits of treatment are unknown. This study investigated the treatment of SCLC in the third-line setting.
  
  
  METHODS
  An international, multicenter retrospective analysis of patients who received at least 3 lines of chemotherapy for their SCLC was performed.
  
  
  RESULTS
  From 2000 to 2010, 120 patients were identified from 5 centers: median age 61, 40% (n = 72) limited stage, and 79% (n = 95) Eastern Cooperative Oncology Group performance status of 0 to 1. Only 22% of these patients received 3 distinct lines of chemotherapy. The remainder were rechallenged with a chemotherapy regimen used at least once previously. Six percent received platinum-based chemotherapy in all 3 lines. In third-line, response rate was 18% and median overall survival was 4.7 months. Factors associated with longer survival included normal baseline LDH levels and response to second-line chemotherapy. On multivariate analysis only normal baseline LDH retained statistical significance. Thirty-five patients went on to receive chemotherapy beyond the third line.
  
  
  CONCLUSIONS
  Few SCLC patients receive 3 chemotherapy lines. Most patients were rechallenged with a similar regimen at least once. Response and survival in the third-line setting are modest. Lack of response to second-line chemotherapy and elevated baseline LDH level might predict lack of benefit from third-line treatment. This data set does not include patients receiving fewer lines for comparison.
authors.affiliation: Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Demetrios
authors.initials: D
authors.lastname: Simos
authors.affiliation: Division of General Internal Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Golmehr
authors.initials: G
authors.lastname: Sajjady
authors.affiliation: Department of Internal Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Sergi
authors.affiliation: Joint Austin-Ludwig Oncology Unit, Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, Australia.
authors.forename: Mun Sem
authors.initials: MS
authors.lastname: Liew
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Califano
authors.affiliation: Division of Medical Oncology, The British Columbia Cancer Agency and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ho
authors.affiliation: Division of Medical Oncology, Princess Margaret Hospital Cancer Centre/University Health Network and University of Toronto, Toronto, Ontario, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Leighl
authors.affiliation: Joint Austin-Ludwig Oncology Unit, Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: White
authors.affiliation: Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Summers
authors.affiliation: The Ottawa Hospital Research Institute, Clinical Epidemiology Program, Methods Centre, Ottawa, Ontario, Canada.
authors.forename: William
authors.initials: W
authors.lastname: Petrcich
authors.affiliation: Division of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. Electronic address: pwheatleyprice@toh.on.ca.
authors.forename: Paul
authors.initials: P
authors.lastname: Wheatley-Price
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
keywords: Outcomes; Retrospective review; Small cell lung cancer; Third-line; Treatment