Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer

Abstract

15041 Background: This study was designed to assess whether a short course of induction therapy with bevacizumab (B) and FOLFOX chemotherapy followed by concurrent B and preoperative chemoradiation (chemoXRT) with weekly oxaliplatin (OX) and continuous infusion (CI) 5-fluorouracil (5-FU) would increase the pathologic complete response (pCR) rate at surgery in patients (pts) with stage II-III rectal cancer. Methods: Pts received 2 biweekly courses of B 5 mg/kg and modified FOLFOX6 followed by B 5 mg/kg q2wks, OX 50 mg/m2 weekly (subsequently reduced to 40 mg/m2/week due to an unacceptably high incidence of grade 3 diarrhea), and CI 5-FU 200 mg/m2/day concurrent with 50.4 Gy pelvic radiation over 6 weeks. Surgical resection was performed between 4 and 8 weeks after completion of preoperative chemoXRT. Adjuvant chemotherapy, consisting of 6 biweekly course of B/modified FOLFOX6, was initiated 4–12 weeks after surgery. Results: Twenty-three pts have been enrolled with a median age of 50. 14 pts had nodal disease by clinical staging. One pt chose alternative therapy and is not evaluable, and another developed a grade 4 arrhythmia during induction therapy and was removed from the study. There were no other grade 3–4 toxicities during the induction B/FOLFOX. In contrast, 15 of 20 pts (75%) developed at least one grade 3 toxicity during chemoXRT, including diarrhea (9 pts), neutropenia (4 pts), pain (3 pts), fatigue, nausea, and radiation dermatitis (2 pts each) and menorrhagia (1 pt). Grade 4 toxicities were limited to one episode of neutropenia and one pt with nausea, diarrhea and weight loss. Five of 20 pts who have undergone surgery had a pCR (25%). Only one pt has relapsed following treatment. Conclusions: Induction B/FOLFOX is well tolerated by pts with stage II-III rectal cancer, while concurrent B/OX/5- FU/XRT is associated with significant gastrointestinal toxicities, that may be related to OX. The addition of induction B/FOLFOX and B/OX to conventional 5-FU/XRT has not clearly increased the pCR. However, while follow-up is short, there may be an impact on preventing systemic recurrence. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, sanofi-aventis Genentech™ BioOncology, sanofi-aventis