Phase II study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-FU, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: A trial of the Eastern Cooperative Oncology Group (E3204).

Abstract

3605 Background: Oxaliplatin and bevacizumab potentiate the antitumor activity of fluoroyprimidines and radiotherapy in preclinical and clinical studies of colorectal cancer. This phase II trial evaluated the efficacy of the preoperative combination of capecitabine, oxaliplatin, and bevacizumab with radiotherapy in rectal cancer. Methods: Eligibility: resectable T3/T4 adenocarcinoma of the rectum ≤ 12 cm. from anal verge. Preoperative treatment was capecitabine (825 mg/m² bid M-F), oxaliplatin (50 mg/m² weekly), bevacizumab (5 mg/kg D1,15,29), and pelvic external beam radiotherapy (50.4 Gy/28 fractions). Surgery was performed within 6-8 weeks. Within 12 weeks of surgery, patients received 12 cycles of FOLFOX + bevacizumab (5 mg/kg) Q2 weeks. Pathologic complete response (path CR) was the primary endpoint. Secondary endpoints included resection rate and toxicity. Results: Fifty-seven patients (pts) enrolled from 7/06 to 5/10 and 54 were eligible. Clinical staging: T3/4 (50/4), NX0/1/2 (2/16/31/5). Most common grade 3/4 non-hematologic toxicities during treatment were rectal pain (9), fatigue (8), and diarrhea (7). Two patients died of aspiration. Nine pts had early postsurgical complications (9 wound infections, 6 dehiscence, 1 abscess) and 23 had late surgical complications (23 non-healing wounds, 12 dehiscence, 5 bowel obstruction/ileus, 2 abscess). Pathologic staging: T0/1/2/3 (11/3/15/19), N0/1/2 (32/10/7). Nine pts had path CRs (17%, 90% CI:[9%-27%]. Surgery was LAR (38) and APR (11). Twenty-two pts did not receive postoperative chemotherapy (39%), 16 due to adverse events. Five local recurrences have been reported. RFS and OS data are immature. Conclusions: The addition of oxaliplatin and bevacizumab to capecitabine and radiotherapy for locally advanced rectal cancer resulted in downstaging for the majority of pts but did not improve the pathologic complete response rate compared to historical controls. The combination resulted in significant early and late postsurgical complications.