title: Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups.
abstract: OBJECTIVE
  Adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC) is now accepted on the basis of several randomized clinical trials (RCTs) that demonstrated improved survival. Although there is strong evidence that adjuvant chemotherapy is effective in stages II and IIIA NSCLC, its utility in stage IB disease is unclear. This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC.
  
  
  METHODS
  Within 4 to 8 weeks of resection, patients were randomly assigned to adjuvant chemotherapy or observation. Eligible patients had pathologically confirmed T2N0 NSCLC and had undergone lobectomy or pneumonectomy. Chemotherapy consisted of paclitaxel 200 mg/m(2) intravenously over 3 hours and carboplatin at an area under the curve dose of 6 mg/mL per minute intravenously over 45 to 60 minutes every 3 weeks for four cycles. The primary end point was overall survival.
  
  
  RESULTS
  Three hundred-forty-four patients were randomly assigned. Median follow-up was 74 months. Groups were well-balanced with regard to demographics, histology, and extent of surgery. Grades 3 to 4 neutropenia were the predominant toxicity; there were no treatment-related deaths. Survival was not significantly different (hazard ratio [HR], 0.83; CI, 0.64 to 1.08; P = .12). However, exploratory analysis demonstrated a significant survival difference in favor of adjuvant chemotherapy for patients who had tumors > or = 4 cm in diameter (HR, 0.69; CI, 0.48 to 0.99; P = .043).
  
  
  CONCLUSIONS
  Because a significant survival advantage was not observed across the entire cohort, adjuvant chemotherapy should not be considered standard care in stage IB NSCLC. Given the magnitude of observed survival differences, CALGB 9633 was underpowered to detect small but clinically meaningful improvements. A statistically significant survival advantage for patients who had tumors > or = 4 cm supports consideration of adjuvant paclitaxel/carboplatin for stage IB patients who have large tumors.
authors.affiliation: Tufts Medical Center, Division of Medical Oncology, Tufts-NEMC, Boston, MA 02111, USA. gstrauss@tuftsmedicalcenter.org
authors.forename: Gary M
authors.initials: GM
authors.lastname: Strauss
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Michael A
authors.initials: MA
authors.lastname: Maddaus
authors.forename: David W
authors.initials: DW
authors.lastname: Johnstone
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Johnson
authors.forename: David H
authors.initials: DH
authors.lastname: Harpole
authors.forename: Heidi H
authors.initials: HH
authors.lastname: Gillenwater
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Watson
authors.forename: David J
authors.initials: DJ
authors.lastname: Sugarbaker
authors.forename: Richard L
authors.initials: RL
authors.lastname: Schilsky
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019370:Observation; D017239:Paclitaxel / Q000008:administration & dosage; D018579:Patient Selection; D011013:Pneumonectomy; D018570:Risk Assessment; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D016190:Carboplatin; D017239:Paclitaxel