title: RTOG 0417: efficacy of bevacizumab in combination with definitive radiation therapy and cisplatin chemotherapy in untreated patients with locally advanced cervical carcinoma.
abstract: OBJECTIVE
  Radiation Therapy Oncology Group 0417 was a phase II study that explored the safety and efficacy of the addition of bevacizumab to chemoradiation therapy. The safety results have been previously reported. Herein we report the secondary efficacy endpoints of overall survival (OS), locoregional failure (LRF), para-aortic nodal failure (PAF), distant failure (DF), and disease-free survival (DFS).
  
  
  METHODS
  Eligible patients with bulky Stage IB-IIIB disease were treated with once-weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic radiation therapy and brachytherapy. Bevacizumab was administered at 10 mg/kg intravenously every 2 weeks for 3 cycles during chemoradiation. For OS, failure was defined as death of any cause and was measured from study entry to date of death. LRF was defined as any failure in the pelvis. PAF was defined as any para-aortic nodal failure. DF was analyzed both including and excluding PAF. DFS was measured from study entry to date of first LRF. DF was measured with or without PAF or death. OS and DFS were estimated by the Kaplan-Meier method, and LRF and DF rates were estimated by the cumulative incidence method.
  
  
  RESULTS
  49 eligible patients from 28 institutions were enrolled between 2006 and 2009. The median follow-up time was 3.8 years (range, 0.8-6.0 years). The surviving patients had a median follow-up time of 3.9 years (range, 2.1-6.0 years). Most patients had tumors of International Federation of Gynecology and Obstetrics Stage IIB (63%), and 80% were squamous. The 3-year OS, DFS, and LRF were 81.3% (95% confidence interval [CI], 67.2%-89.8%), 68.7% (95% CI, 53.5%-79.8%), and 23.2% (95% CI, 11%-35.4%), respectively. The PAF, DF without PAF, and DF with PAF at 3 years were 8.4% (95% CI, 0.4%-16.3%), 14.7% (95% CI, 4.5%-24.9%), and 23.1% (95% CI 11.0%-35.2%), respectively.
  
  
  CONCLUSIONS
  In this study, bevacizumab in combination with standard pelvic chemoradiation therapy for locally advanced cervical cancer showed efficacy results that are promising and may warrant further investigation.
authors: University of Colorado, Denver, Aurora, Colorado. Electronic address: tracey.schefter@ucdenver.edu.
authors: Tracey
authors: T
authors: Schefter
authors: RTOG Statistical Center, Philadelphia, Pennsylvania.
authors: Kathryn
authors: K
authors: Winter
authors: University of British Columbia and BC Cancer Agency, Vancouver, British Columbia.
authors: Janice S
authors: JS
authors: Kwon
authors: University of Colorado, Denver, Aurora, Colorado.
authors: Kelly
authors: K
authors: Stuhr
authors: King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors: Khalid
authors: K
authors: Balaraj
authors: Western University, London Regional Cancer Program, London, Ontario.
authors: Brian Patrick
authors: BP
authors: Yaremko
authors: Loyola University Chicago Stritch School of Medicine, Chicago, Illinois.
authors: William
authors: W
authors: Small
authors: Intermountain Medical Center, Murray, Utah.
authors: William
authors: W
authors: Sause
authors: University of Utah Health Sciences Center, Salt Lake City, Utah.
authors: David
authors: D
authors: Gaffney
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D018196:Carcinoma, Adenosquamous / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D016001:Confidence Intervals; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D002945:Cisplatin