Neoadjuvant bevacizumab, capecitabine, and radiotherapy in locally advanced rectal cancer: Interim results of a phase II CRAB trial.

Abstract

e14006 Background: Preoperative capecitabine-based chemoradiation (CRT) is a standard treatment for locally advanced rectal cancer. The radiosensitizing effect of bevacizumab (Bev), an inhibitor of the angiogenesis pathways, may further enchance tumor regression. This prospective, nonrandomized phase II study evaluated the efficacy and safety of Bev combined with capecitabine and concurrent RT for locally advanced rectal cancer. Methods: Patients (pts) with stage II or III rectal cancer confirmed by MRI were treated with an infusion of Bev (5 mg/kg) 2 weeks prior to neoadjuvant CRT, followed by Bev 5 mg/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. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathologic response (pCR). Results: Twenty-six of 39 pts enrolled so far were eligible for safety and efficacy analyses. Median age was 57 (range: 31–74) years, 65% of pts were male. Six pts (23%) had T3N0 tumors, 6 pt (23%) T3N1, 2 pt (8%) T2N2, 9 pts (35%) T3N2, and 3 pts (11%) T4N2. In 11 pts (43%) tumor invaded the mesorectal fascia. The median tumor distance from anal verge was 5 (range: 1–11) cm. All pts received 50.4 Gy RT and 4 Bev infusions. Temporary capecitabine intake interruption was necessary for 1 (3.8%) due to leucopenia grade 2. Grade 3 toxicities included dermatitis (n = 5, 19.2%), diarrhea (n = 1, 3.8%) and proteinuria (n = 2, 7.7%). Nineteen patients (73%) had sphincter preserving surgery and in 1 pt exploration only was performed because of carcinosis of peritoneum. TRG 4 (pCR) was recorded in 4/25 pts (16%) and TRG 3 in 4 pts (16%). T-, N- and overall downstaging rates were 56%, 68% and 76%, respectively. Conclusions: Preoperative CRT with bevacizumab and capecitabine is safe and feasible. The high pathologic downstaging rate is promising, although so far, the pCR rate appeared to be lower than previously reported by some investigators. No significant financial relationships to disclose.