title: Comparative outcomes of squamous and non-squamous non-small cell lung cancer (NSCLC) patients in phase II studies of ASA404 (DMXAA) - retrospective analysis of pooled data.
abstract: BACKGROUND
  ASA404 (5,6-dimethylxanthenone-4-acetic acid) is a small-molecule, flavonoid tumor-vascular disrupting agent. Pooled data from phase II studies were analyzed retrospectively to compare safety and efficacy between squamous and non-squamous non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  Data from previously untreated patients with stage IIIb/IV NSCLC who were randomized to receive up to six cycles of carboplatin (C; AUC 6 mg/ml•min) and paclitaxel (P; 175 mg/m(2)) alone or with ASA404 (1200 mg/m(2)), or enrolled in an extension study to receive CP and ASA404 (1800 mg/m(2)), were analyzed. Differences between subgroups were calculated using Fisher's exact test.
  
  
  RESULTS
  Of the 108 enrolled patients, safety data from the 104 patients included in the safety population were pooled to compare results between histological subgroups (squamous vs non-squamous) and treatment (CP alone vs CP + ASA404). Addition of ASA404 to the standard chemotherapy regimen did not appear to substantially increase toxicity, and there were no serious adverse events associated with bleeding, pulmonary hemorrhage, or hemoptysis. Activity with CP + ASA404 appeared improved over CP alone, with median survival 10.2 vs 5.5 months in squamous, and 14.9 vs 11.0 months in non-squamous populations, respectively.
  
  
  CONCLUSIONS
  This analysis is limited by its retrospective nature, and by the small size of the overall group, treatment and disease subgroups. However, as ASA404 appears to have a similar safety and activity profile in patients with squamous and non-squamous NSCLC, the findings support inclusion of both groups of patients in ongoing definitive phase III trials of ASA404 (NCT00832494).
authors.affiliation: The University of Auckland, Auckland 1023, New Zealand;
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McKeage
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jameson