Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer
Authors: T. Dipetrillo, V. Pricolo, J. Lagares-Garcia, W. Sikov, M. Vrees, B. McNulty, B. O'Connor, A. Klipfel, H. Khurshid, H. Safran
Journal: Journal of Clinical Oncology (2009)

4105^ Background: This study evaluates induction bevacizumab and FOLFOX followed by concurrent chemoradiotherapy (CRT) with bevacizumab, weekly oxaliplatin, and continuous infusion 5-FU prior to surgical resection of newly-diagnosed Stage II or III rectal cancer. Methods: Eligible patients received one month of induction, biweekly bevacizumab (5mg/kg) and modified FOLFOX6. Patients then received 50.4Gy of radiation and concurrent bevacizumab (5 mg/kg on days 1, 15, and 29), oxaliplatin (50 mg/m 2 /week for 6 weeks), and 5-FU (200mg/m 2 /day) as a continuous IV infusion throughout radiation. Due to gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m 2 /week. Resection was performed 4 to 8 weeks after the completion of CRT. Adjuvant chemotherapy was started after 4 but less than 12 weeks following surgical resection and consisted of 6 biweekly treatments of modified FOLFOX6 and bevacizumab. Results: Twenty-six eligible patients were treated. The median age was 50. One patient developed a grade 4 arrhythmia during induction chemotherapy and was removed from the study. Of the remaining 25 patients, there were no other grade 3 or 4 toxicities during induction FOLFOX/bevacizumab. Toxicity was more significant during chemoradiation. Any grade 3 toxicity was experienced by 19 of 25 (76%) patients. Grade 3 toxicities included diarrhea (40%), neutropenia (16%), pain (16%), fatigue (8%), nausea (8%), and radiation dermatitis (8%) and bleeding with menstruation (4%). Grade 4 toxicities included neutropenia (4%), sepsis (4%) and nausea/diarrhea (4%). Six of 25 resected patients (24%) had a complete pathologic response. Eight of 25 patients (32%) developed post-operative wound complications including infection/abscess (n=4), fistula (n=2), ischemic colonic reservoir (n=1) and sterile fluid collection (n=1). Nine of 25 (36%) patients developed postoperative wound complications including infection (n=4), delayed healing (n=3), leak/abscess (n=2), sterile fluid collection (n=2), ischemic colonic reservoir (n=1), and fistula (n=1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen to similar to other fluorouracil based chemoradiaton regimens. The high incidence of post-operative wound complications is concerning and consistent with other reports utilizing bevacizumab prior to major surgical resections. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .