Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer
Authors: Dipetrillo T. , Pricolo V. , Lagares-Garcia J. , Sikov W. , Vrees M. , McNulty B. , O'Connor B. , Klipfel A. , Khurshid H. , Safran H. 
Published: August 2020

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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/m2/week for 6 weeks), and 5-FU (200mg/m2/day) as a continuous IV infusion throughout radiation. Due to gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m2/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.

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