title: Patients treated with platinum-doublet chemotherapy for advanced non--small-cell lung cancer have inferior outcomes if previously treated with platinum-based chemoradiation.
abstract: BACKGROUND
  The standard of care for locoregionally advanced non-small-cell lung cancer is concurrent platinum-based chemoradiation. Many patients relapse, and subsequent systemic treatment may involve platinum-doublet chemotherapy. It is not known if prior platinum-based chemoradiation influences the response to platinum-based chemotherapy given subsequently for relapse. Therefore, we compared outcomes in these patients with those in patients without prior treatment.
  
  
  METHODS
  A retrospective study of patients who had been treated with carboplatin and gemcitabine chemotherapy for de novo metastatic disease or recurrent non--small-cell lung cancer after receiving platinum-based chemoradiation. The primary outcome was progression-free survival (PFS).
  
  
  RESULTS
  A total of 104 patients were analyzed. The median age was 63 years (range, 35-81 years), with 63 (61%) patients with newly diagnosed disease and with 41 (39%) who were previously treated. The response rate was significantly lower for those previously exposed to chemoradiation (10% vs. 29%: P = .001), as was the median PFS (3.6 months vs. 5.7 months; P = .002), and median overall survival (OS) (8.6 months vs. 12.1 months; P = .007). Only the treatment group was a significant predictor (P = .032) of PFS by univariate analysis. In univariate analysis; sex (men; P = .04), histology (squamous cell; P = .04), Eastern Cooperative Oncology Group Performance Status Scale (P = .002), and treatment group (P = .023) predicted significantly inferior OS. Multivariate analysis showed that performance status was the only significant predictor of inferior OS.
  
  
  CONCLUSIONS
  Outcomes were inferior in patients previously exposed to platinum-based chemoradiation. An approach of stratifying such patients in future trials of chemotherapy should be adopted. Alternative options such as non--platinum-based agents or targeted therapies should be considered in this group.
authors.affiliation: Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
authors.forename: Ashvin
authors.initials: A
authors.lastname: Paramanathan
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
authors.forename: Marnie
authors.initials: M
authors.lastname: Collins
authors.forename: Michael
authors.initials: M
authors.lastname: Franco
authors.forename: Sarah
authors.initials: S
authors.lastname: Kofoed
authors.forename: Heather
authors.initials: H
authors.lastname: Francis
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D016022:Case-Control Studies; D059248:Chemoradiotherapy / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Chemoradiation; Non–small-cell lung cancer; Platinum resistance