title: Restrictive eligibility limits access to newer therapies in non-small-cell lung cancer: the implications of Eastern Cooperative Oncology Group 4599.
abstract: BACKGROUND
  In a previous randomized phase II trial evaluating carboplatin and paclitaxel with or without bevacizumab in patients naive to chemotherapy with advanced non-small-cell lung cancer (NSCLC), median survival ranged from 53 weeks to 76 weeks. Sudden life-threatening hemoptysis occurred in 6 of 66 patients receiving chemotherapy and bevacizumab; 4 episodes were fatal, all in patients with squamous cell histology. Squamous histology and bevacizumab therapy were the only factors associated with life-threatening hemorrhage. ECOG 4599 (Eastern Cooperative Oncology Group 4599), a randomized phase III trial of paclitaxel and carboplatin with or without bevacizumab ultimately excluded patients with squamous histology as well as brain metastases, ongoing therapeutic anticoagulation/nonsteroidal anti-inflammatory drugs, antecedent hemoptysis, and performance status (PS) of 2.
  
  
  METHODS
  We performed a retrospective analysis during a defined period to determine the proportion of patients with newly evaluated advanced NSCLC seen at Fox Chase Cancer Center (FCCC) who would have been eligible for ECOG 4599. We reviewed new thoracic oncology patient visits (n = 260) at FCCC scheduled with 6 medical oncologists from March 1, 2002, through August 8, 2002.
  
  
  RESULTS
  Forty-five patients had histology that made them ineligible (8 mesothelioma, 6 small-cell, 5 mixed histology, and 26 non-lung cancers). Of the remaining 215 patients with NSCLC, 8 had incomplete charts for review and 7 had stage I, 8 stage II, and 43 stage III NSCLC. Of the remaining 149 patients, 33 had received chemotherapy previously. Of the remaining 116, only 34 (29.3%) were eligible. Of 82 ineligible patients, 21 (25.6%) had PS > or = 2, 20 (24.3%) had central nervous system (CNS) metastases, 11 (13.4%) had squamous histology, 9 (10.9%) had therapeutic anticoagulation, and 21 (25.6%) had > or = 2 criteria (11 PS > or = 2/squamous histology; 3 PS > or = 2/CNS involvement; 2 PS > or = 2/anticoagulation, 2 CNS metastasis/anticoagulation, 2 PS > or = 2/squamous histology/anticoagulation, 1 PS > or = 2/squamous histology/CNS metastasis). Of 34 eligible patients, only 6 (17.6%) enrolled in the trial.
  
  
  CONCLUSIONS
  Based on the data reviewed, > 70% of patients who might otherwise have been eligible for standard advanced NSCLC trials were not candidates for ECOG 4599. Outcome with respect to this study must be interpreted in the context of eligibility restrictions.
authors.affiliation: Department of Medical Oncology, Cooper Medical Center, Cherry Hill, NJ, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Somer
authors.forename: Eric
authors.initials: E
authors.lastname: Sherman
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D004608:Eligibility Determination; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D015337:Multicenter Studies as Topic; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016190:Carboplatin; D017239:Paclitaxel