title: A phase 2 randomized trial of paclitaxel and carboplatin with or without panitumumab for first-line treatment of advanced non-small-cell lung cancer.
abstract: BACKGROUND
  This two-part phase 2 study evaluated the efficacy and safety of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, combined with carboplatin/paclitaxel in patients with previously untreated advanced non-small-cell lung cancer.
  
  
  METHODS
  In part 1, patients were sequentially enrolled to receive paclitaxel 200 mg/m(2) and carboplatin (area under the concentration-versus-time curve, 6 mg/min/ml) plus panitumumab (1.0, 2.0, or 2.5 mg/kg). In part 2, patients were randomized 2:1 to receive paclitaxel/carboplatin with (arm A) or without (arm B) the maximum tolerated dose of panitumumab identified in part 1. Primary endpoints in parts 1 and 2 were the incidence of dose-limiting toxicities and time to progression (TTP), respectively.
  
  
  RESULTS
  In part 1, four of 19 patients had dose-limiting toxicities: three at 2.0 mg/kg (fatigue, pain in extremity, dyspepsia) and one at 2.5 mg/kg (rash). The maximum tolerated dose was not reached; panitumumab 2.5 mg/kg was selected for part 2. In part 2, TTP was 18.1 weeks (95% confidence interval [CI], 13.6-23.3) in arm A and 23.0 weeks (95% CI, 15.9-24.1) in arm B (hazard ratio, 0.9; 90% CI, 0.66-1.21; p = 0.555). Progression-free survival in arms A and B was 17.6 weeks and 18.3 weeks, respectively, and the objective response rate was 15.2% and 11.1%. Adverse events occurring more frequently in arm A than in arm B included skin toxicity, diarrhea, stomatitis, vomiting, and dizziness. Exploratory analyses did not demonstrate associations between potential biomarkers and outcomes.
  
  
  CONCLUSIONS
  Although toxicity was predictable and manageable, the addition of panitumumab to paclitaxel/carboplatin did not improve TTP in patients with previously untreated advanced non-small-cell lung cancer.
authors.affiliation: *Department of Medicine, Duke University Medical Center, Durham, North Carolina; †Hematology Oncology Associates, Port St. Lucie, Florida; ‡Department of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana; §Oregon Health and Science University, Portland, Oregon; ‖Illinois CancerCare, Peoria, Illinois; ¶Departments of Global Biostatistical Science, Oncology Research, and Global Safety, Amgen Inc., Thousand Oaks, California; and #Division of Hematology and Medical Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.forename: Paul
authors.initials: P
authors.lastname: Swanson
authors.forename: Paul
authors.initials: P
authors.lastname: Schwarzenberger
authors.forename: Alan
authors.initials: A
authors.lastname: Sandler
authors.forename: Diane
authors.initials: D
authors.lastname: Prager
authors.forename: Kathy
authors.initials: K
authors.lastname: Zhang
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Freeman
authors.forename: Carol W
authors.initials: CW
authors.lastname: Johnson
authors.forename: Kartik
authors.initials: K
authors.lastname: Krishnan
authors.forename: David
authors.initials: D
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D000077544:Panitumumab; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D016190:Carboplatin; D017239:Paclitaxel