Phase II Study of Preoperative Concurrent Chemoradiotherapy with S-1 plus Bevacizumab for Locally Advanced Resectable Rectal Adenocarcinoma

Abstract

Objective: A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of preoperative chemoradiotherapy (CRT) with concurrent S-1, bevacizumab, and radiation in patients with locally advanced rectal cancer (LARC). Methods: Fifty-two patients with LARC were enrolled. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, S-1 was administered orally twice a day on days 1-14 and 22-35, and bevacizumab was administered on days 1, 15, and 29. Surgical resection was scheduled 8 weeks (6-10 weeks) after completing the CRT. Results: All 52 patients underwent R0 radical surgery. Sphincter preservation was possible in 38 (73.1%) patients. A pathologic complete response was obtained in 10 (19.2%) patients, a pathologic downstaging was achieved in 37 (71.2%) patients, and the tumor shrinkage rate was 77.1%. The only grade 3 adverse events were leukopenia and rash in 1 (1.9%) patient. The rate of postoperative complications was 28.8%. Anastomotic leakage occurred in 9 (23.7%) of the 38 patients who underwent sphincter-preserving surgery. Perineal wound dehiscence developed in 2 (14.3%) of the 14 patients who received an abdominoperineal resection. Conclusions: Adding bevacizumab to S-1 clearly increased the incidence of wound-related complications, with no distinct enhancement of tumor response. i 2014 S. Karger AG, Basel

Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial

“…Findings of one study 21 showed that bevacizumab has sustained effects on VEGF inhibition more than 6 weeks after dosing, and findings of several rectal cancer trials in which bevacizumab was used in conjunction with neoadjuvant chemotherapy or chemoradiotherapy showed increased rates of post-operative complications 22, 23, 24, 25. Tumour and blood specimens were collected at baseline in this trial and will be used to investigate whether patients susceptible to long-term effects of bevacizumab such as impaired wound healing can be identified.…”

Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial

“…We initially used oral UFT and subsequently used oral UFT plus leucovorin to perform clinical phase I and II studies. We also used oral S-1 and bevacizumab to conduct a clinical phase II study and reported that 24-h biweekly intravenous infusion of irinotecan combined with FUs (UFT or UFT plus leucovorin), S-1, and bevacizumab is useful with acceptable adverse events [8, 9, 14].…”

Combining radiotherapy with sunitinib: lessons (to be) learned

“…Differences in dose scheduling, type of drug, and tumor type will influence the therapeutic efficacy [ 76 ]. For example, the combination of bevacizumab (anti-VEGF antibody) and RTx can induce encouraging response rates [ 77 , 78 ] or increased toxicity without any response [ 79 , 80 ]. Similar divergent responses have been described for the combination of RTx with sorafenib, a TKI that targets several angiogenesis-related proteins, including VEGFR, PDGFR, and Raf kinases [ 81 – 83 ].…”