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.
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Authors | C Borg, T André, G Mantion, F Boudghène, F Mornex, P Maingon, A Adenis, D Azria, M Piutti, O Morsli, J F Bosset |
Journal | Annals of oncology : official journal of the European Society for Medical Oncology
(Ann Oncol)
Vol. 25
Issue 11
Pg. 2205-2210
(Nov 2014)
ISSN: 1569-8041 [Electronic] England |
PMID | 25122693
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]. |
Chemical References |
- Antibodies, Monoclonal, Humanized
- Organoplatinum Compounds
- Oxaliplatin
- Deoxycytidine
- Bevacizumab
- Leucovorin
- Fluorouracil
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Topics |
- Adolescent
- Adult
- Aged
- Antibodies, Monoclonal, Humanized
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage)
- Bevacizumab
- Deoxycytidine
(administration & dosage)
- Digestive System Surgical Procedures
- Female
- Fluorouracil
(administration & dosage)
- Humans
- Leucovorin
(administration & dosage)
- Magnetic Resonance Imaging
- Male
- Middle Aged
- Neoadjuvant Therapy
- Neoplasm Recurrence, Local
(drug therapy, pathology, radiotherapy, surgery)
- Organoplatinum Compounds
(administration & dosage)
- Oxaliplatin
- Rectal Neoplasms
(drug therapy, pathology, radiotherapy, surgery)
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