title: Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410.
abstract: BACKGROUND
  The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.
  
  
  METHODS
  A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with 63 Gy TRT delivered as once-daily fractions beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily fractions beginning on day 1 [corrected]. Arm 3 used cisplatin at 50 mg/m2 on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan-Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided.
  
  
  RESULTS
  Median survival times were 14.6, 17.0, and 15.6 months for arms 1-3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3-5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar.
  
  
  CONCLUSIONS
  Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.
authors: Department of Radiation Oncology and Winship Cancer Institute, Emory University, 1365C Clifton Rd, NE, Ste C4104, Atlanta, GA 30322, USA. wcurran@emory.edu
authors: Walter J
authors: WJ
authors: Curran
authors: Rebecca
authors: R
authors: Paulus
authors: Corey J
authors: CJ
authors: Langer
authors: Ritsuko
authors: R
authors: Komaki
authors: Jin S
authors: JS
authors: Lee
authors: Stephen
authors: S
authors: Hauser
authors: Benjamin
authors: B
authors: Movsas
authors: Todd
authors: T
authors: Wasserman
authors: Seth A
authors: SA
authors: Rosenthal
authors: Elizabeth
authors: E
authors: Gore
authors: Mitchell
authors: M
authors: Machtay
authors: William
authors: W
authors: Sause
authors: James D
authors: JD
authors: Cox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015986:Confounding Factors, Epidemiologic; D018450:Disease Progression; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin