title: Third-line chemotherapy in advanced non-small cell lung cancer: identifying the candidates for routine practice.
abstract: BACKGROUND
  The interest of first- and second-line treatments in non-small cell lung cancer (NSCLC) has been demonstrated by successive randomized trials. Improvements in lung cancer care have routinely allowed a significant proportion of patients to be considered for third-line treatment.
  
  
  METHODS
  A retrospective analysis was performed, including all consecutive patients with advanced NSCLC, who received at least three lines of systemic antineoplastic treatment at our institution.
  
  
  RESULTS
  From a population of 613 patients treated with first-line treatment, a total of 173 patients received third-line treatment (cytotoxic chemotherapy in 131 patients; epidermal growth factor (EGFR) tyrosine kinase inhibitors in 42 patients). Only 13 patients (8%) received less than 75% of the theoretical dose intensity; 22 patients (13%) presented with severe toxicities. Symptom relief and performance status (PS) improvement were observed in 121 (92% of the 131 patients with symptoms) and 90 patients (52%), respectively. Using multivariate analysis, survival after third-line treatment was significantly increased in patients younger than 70 years-old (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.53-0.99, p = 0.047), who smoked less than 10 pack-years (HR = 0.82, 95% CI: 0.57-0.93, p = 0.036), with no cancer-related symptoms (HR = 0.75, 95% CI: 0.61-0.92, p = 0.007), a weight loss inferior to 5 kg since the beginning of second-line (HR = 0.63, 95% CI: 0.52-0.75, p = 0.013), a PS 0 to 1 (HR = 0.81, 95% CI: 0.76-0.86, p = 0.008), and no extrathoracic tumor spread at initiation of third-line treatment (HR = 0.67, 95% CI: 0.47-0.94, p = 0.042). Disease control after both first- and second-line treatments was the strongest predictor of prolonged survival after third-line treatment (HR = 0.47, 95% CI: 0.33-0.67, p = 0.001).
  
  
  CONCLUSIONS
  Patients with advanced NSCLC may benefit from third-line treatment. The best candidates can be identified using standard prognostic factors, such as PS, and disease control after first- and second-line treatments.
authors.affiliation: Service de Pneumologie, Centre Hospitalier Universitaire de Besançon, Université de Franche Comté, Besançon, France. nggirard@gmail.com
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Pascale
authors.initials: P
authors.lastname: Jacoulet
authors.forename: Marie
authors.initials: M
authors.lastname: Gainet
authors.forename: Rami
authors.initials: R
authors.lastname: Elleuch
authors.forename: Didier
authors.initials: D
authors.lastname: Pernet
authors.forename: Alain
authors.initials: A
authors.lastname: Depierre
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Dalphin
authors.forename: Virginie
authors.initials: V
authors.lastname: Westeel
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D000068437:Pemetrexed; D011379:Prognosis; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; D006147:Guanine; D000093542:Gemcitabine