P-0287 Prospective Trial of Synchronous Capecitabine, Radiotherapy and Bevacizumab for Locally Advanced Rectal Cancer (Crab)

Abstract

ABSTRACT Introduction Neoadjuvant capecitabine based chemoradiotherapy and radical surgery are considered to be optimal treatment approach to locally-advanced rectal cancer. We assessed the efficacy and safety of adding targeting agent bevacizumab to this standard treatment to increase the pathological complete remission rate of locally advanced rectal cancer as primary end point. Secondary end points were survival parameters and quality of life. Methods Enrolled patients (pts) with MRI-confirmed stage II/III rectal cancer were treated with an infusion of Bev (5 mg/kg) 2 weeks prior to neoadjuvant CRT, followed by Bev 5mg/m2 on week 3, 5, 7 and capecitabine 825 mg/m2 bid including weekends during RT. RT was administered at 50.4 Gy (25×1.8 Gy with boost 3×1.8 Gy, 3D conformal technique), starting on week 3. Total mesorectal excision was scheduled 6-8 weeks after completion of CRT. Surgery was conducted 6-8 weeks following CRT, with post-operative chemotherapy with capecitabine (1250 mg/m2 twice daily for 14 days every 21 days). Results Results A total of 60 pts were eligible for analysis: median age was 60 years(range: 31–79) years, 64% of pts were male. The most frequent MRI stage was T3 (87%) and N+(80%). The median tumor distance from anal verge was 6 (range: 0–11) cm. The grade 3 toxic effects were leukopenia (n=3), diarrhea (n=1), dermatitis (n=6), proteinuria (n=4) and hypertension (n=1). and one grade 4 vascular toxicity. Radical resection was achieved in 58 pts (96.7%) TRG 4 (pCR) was recorded in 8 pts (13.3%) and TRG 3 in 9 pts (15%). Fifty pts received capecitabine postoperatively. (83.3%). Perioperative adverse events (within 30 days after surgery) were recorded in thirty-eight pts (62.3%): delayed wound healing (n=18, 30%), infection/abscess (n=12, 20%) and anastomotic leak (n=7, 11.7%). Six pts required surgical reintervention for leak (n=3), abdominal abscess (N=2) and pneumothorax (n=1). With longer follow-up, the rate of adverse events was 40% (n=24) and most commonly due to delayed wound healing (n=9, 15%), followed by rectovaginal or uretero perineal fistula (n=4, 6.7%), anastomotic leak (n=2, 3.3%) and intestinal necrosis (n=1, 1.7%). Five pts (8.3%) required re-operation. Median follow-up was 24 months (7-35 months). No pts were lost during follow-up. The 2-year overall survival, disease-free survival, recurrence-free survival and local control rates were 91.4%, 76.2%, 84.9% and 96%, respectively. Conclusion The addition of bevacizumab to conventional capecitabine-based preoperative CRT is tolerable treatment for LARC. Results of our study indicate the potential long-term therapeutic benefit in LARC, although longer follow-up is needed to fully assess survival parameters in this setting. On the other hand, it is associated with high rate of perioperative and postoperative complications. The open question in regard to efficacy, early and late toxicity of this combined modality treatment should be evaluated in large, phase III trial.