Preoperative chemoradiotherapy regimen with capecitabine and bevacizumab in locally advanced rectal cancer: A feasibility study of the Dutch Colorectal Cancer Group (DCCG)

15040 Background: Radiotherapy (RT) combined with 5FU and bevacizumab seems a promising combination for locally advanced rectal cancer, but little data are available regarding toxicity and surgical complications. This multicenter study tests the feasibility of the combination of RT, capecitabine and bevacizumab in rectal cancer patients. Method: 60 patients with a rectal adenocarcinoma with a threatened or involved circumferential resection margin (CRM) will be included. Treatment consists of radiotherapy (50 Gy/25), capecitabine 825 mg/m2 bid and bevacizumab 5 mg /m2 iv on day -14, 1, 15 and 29, with surgery 6–10 weeks thereafter. An interim analysis was scheduled after the inclusion of 15 patients with abdominoperineal resection (APR)/Hartmann procedures. In general, CTC toxicity criteria were used, for local skin toxicity RTOG criteria were used. Results: So far, 23 patients (12 cT3, 11 cT4 tumors) have been entered: 12 APR, 3 Hartmann procedures and 7 low anterior resections (LAR). One patient died before surgery. During chemoradiotherapy (CRT), 7 grade 3 toxicities (4 skin, 2 diarrhea, 1 tenesmi) and one grade 4 toxicity (anal mucositis) were reported. One patient developed an enteritis with diffuse uncontrollable bleeding at the end of the CRT. This patient died before rectal surgery. Two small bowel perforations occurred, with one occurring 70 days after the last administration of bevacizumab. A third patient had an asymptomatic rectal wall perforation at the site of the primary tumor. Surgical complications consisted of one perineal dehiscence, one rectovaginal fistula after a stapling failure and oneperoperative bleeding (5500 cc). Postoperatively, one patient developed a pulmonary embolism. The CRM was negative in 20/22 operated patients. Downstaging of the T-stage was observed in 18/21 patients. Of those, two patients had a complete pathological response, whereas 9 patients had a ypT0–2 tumor. Conclusions: These results indicate that the combination of radiotherapy, capecitabine and bevacizumab is very effective. The observed toxicity pattern warrants further investigation of the relationship between radiation-induced enteritis and small bowel complications. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche