title: Chemotherapy effectiveness after first-line gefitinib treatment for advanced lepidic predominant adenocarcinoma (formerly advanced bronchioloalveolar carcinoma): exploratory analysis of the IFCT-0401 trial.
abstract: OBJECTIVE
  This study explored whether chemotherapy after first-line gefitinib was effective in patients with advanced lepidic predominant adenocarcinoma (LPA), formerly advanced bronchioloalveolar carcinoma, who were enrolled in the Intergroupe Francophone de Cancérologie Thoracique (IFCT)-0401 trial.
  
  
  METHODS
  Overall, 88 patients presenting advanced LPA were enrolled in the IFCT-0401 trial, receiving gefitinib as first-line therapy. No predefined second-line treatment was mandatory in the case of progression or limiting toxicity under gefitinib. However, the carboplatin plus paclitaxel regimen was recommended for patients with a performance status (PS) 0 or 1 and gemcitabine monotherapy for those with a PS 2. For these patients, data concerning treatment efficacy was collected from the IFCT-0401 trial database.
  
  
  RESULTS
  In total, 47 patients (53%) received second-line treatment after the failure of gefitinib, with 43 having PS 0 or 1. Regarding treatment, 43 were treated with chemotherapy, with 38 receiving a platinum-doublet regimen (taxane-based, n = 29; gemcitabine-based, n = 9) and five receiving monotherapy (gemcitabine, n = 3; pemetrexed, n = 2). The overall response rate (ORR) to chemotherapy was 21% (95% confidence interval [CI]: 10-36), disease control rate 56% (95% CI: 40-71), and median progression-free survival (PFS) 3.0 months (95% CI: 2.4-4.9). For patients receiving a platinum doublet (n = 38), ORR was 21% (95% CI: 10-37), with disease control rate being 55% (95% CI: 38-71), and median PFS 2.9 months (95% CI: 2.4-4.4). For patients receiving taxane-based regimen (n = 29) and gemcitabine-based regimen (n = 12), ORR was 28% and 0%, respectively, with a median PFS of 3.3 and 2.0 months, respectively, (p = 0.0243). The two patients receiving pemetrexed experienced a prolonged response. Multivariate Cox model analysis revealed that only the use of taxane-based chemotherapy or pemetrexed was related to PFS.
  
  
  CONCLUSIONS
  Platinum-doublet chemotherapy showed some effectiveness in treating advanced LPA patients after first-line gefitinib. Our findings also suggest that taxane-based chemotherapy and pemetrexed should be investigated further in future clinical trials.
authors: ER2 and GRC-04 Theranoscan, Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France.
authors: Michaël
authors: M
authors: Duruisseaux
authors: Laurence
authors: L
authors: Baudrin
authors: Elisabeth
authors: E
authors: Quoix
authors: Marie
authors: M
authors: Wislez
authors: Denis
authors: D
authors: Moro-Sibilot
authors: Daniel
authors: D
authors: Coëtmeur
authors: Isabelle
authors: I
authors: Monnet
authors: Pierre
authors: P
authors: Mourlanette
authors: Jean-François
authors: JF
authors: Morère
authors: Jean-Charles
authors: JC
authors: Soria
authors: Virginie
authors: V
authors: Westeel
authors: Franck
authors: F
authors: Morin
authors: Jacques
authors: J
authors: Cadranel
mesh_terms: D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; 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; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed; D011379:Prognosis; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D011799:Quinazolines; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D016190:Carboplatin; D017239:Paclitaxel; D000077156:Gefitinib; D000093542:Gemcitabine