skip to main content

Title: Efficacy Endpoints of Radiation Therapy Group Protocol 0247: A Randomized, Phase 2 Study of Neoadjuvant Radiation Therapy Plus Concurrent Capecitabine and Irinotecan or Capecitabine and Oxaliplatin for Patients With Locally Advanced Rectal Cancer

Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m{sup 2}/d Monday-Friday) plus irinotecan (50 mg/m{sup 2}/wk × 4); and (2) capecitabine (1650 mg/m{sup 2}/d Monday-Friday) plus oxaliplatin (50 mg/m{sup 2}/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 to 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m{sup 2}; leucovorin 400 mg/m{sup 2}; 5-fluorouracil 400 mg/m{sup 2}; 5-fluorouracil 2400 mg/m{sup 2}) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local–regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin armmore » was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6] ;  [7] ;  [4] ;  [8] ;  [9] ;  [10] ;  [1] ;  [11]
  1. Medical College of Wisconsin, Madison, Wisconsin (United States)
  2. Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States)
  3. University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio (United States)
  4. Department of Radiation Oncology and Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)
  5. Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts (United States)
  6. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)
  7. Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)
  8. The Schiffler Cancer Center, Wheeling, West Virginia (United States)
  9. Intermountain Medical Center, Murray, Utah (United States)
  10. Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)
  11. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)
Publication Date:
OSTI Identifier:
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 91; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States