C Borg1, T André2, G Mantion3, F Boudghène4, F Mornex5, P Maingon6, A Adenis7, D Azria8, M Piutti9, O Morsli9, J F Bosset10. 1. Department of Medical Oncology, University Hospital of Besançon and CIC-BT506, Besançon. Electronic address: christophe.borg@efs.sante.fr. 2. Department of Medical Oncology, Saint Antoine Hospital and Pierre and Marie Curie University, Paris. 3. Department of Digestive and Liver Surgery, University Hospital of Besançon, Besançon. 4. Department of Radiology, Tenon Hospital, Paris. 5. Department of Radiotherapy, Lyon-Sud Hospital Center, Lyon. 6. Department of Radiotherapy, Georges-François-Leclerc Center, Dijon. 7. Department of Medical Oncology, Oscar Lambret Center, Lille. 8. Department of Radiotherapy, Centre de Lutte Contre le Cancer Val D'Aurelle, Montpellier. 9. Roche Laboratories, Boulogne-Billancourt. 10. Department of Radiotherapy, University Hospital of Besançon, Besançon, France.
Abstract
BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS:Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.
RCT Entities:
BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.
Authors: S Hoendervangers; J P M Burbach; M M Lacle; M Koopman; W M U van Grevenstein; M P W Intven; H M Verkooijen Journal: Ann Surg Oncol Date: 2020-06-10 Impact factor: 5.344
Authors: Maria C Riesco-Martinez; Carlos Fernandez-Martos; Cristina Gravalos-Castro; Paula Espinosa-Olarte; Anna La Salvia; Luis Robles-Diaz; Andrea Modrego-Sanchez; Rocio Garcia-Carbonero Journal: Cancers (Basel) Date: 2020-12-05 Impact factor: 6.639
Authors: Hyuk Hur; Min Soo Cho; Woong Sub Koom; Joon Seok Lim; Tae Il Kim; Joong Bae Ahn; Hoguen Kim; Nam Kyu Kim Journal: Chin J Cancer Res Date: 2020-04 Impact factor: 5.087