Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer

Abstract

Background: Neoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer.Methods: A retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery.Results: The 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months).Conclusions: This modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.

A 73-Year-Old Woman Treated for Rheumatoid Arthritis with Lower Rectal Carcinoma Who Underwent Abdominoperineal Resection, Lateral Regional Lymph Node Resection, and Partial Hepatectomy by Hand-Assisted Laparoscopic Surgery (HALS): A Case Report

“…Therefore, we did not consider mutations in RAS and BRAF [ 27 ]. Our treatment strategy positioned radiation therapy as an optional treatment in case of postoperative local relapse [ 29 ]. However, a recently published Japanese clinical guideline recommends deciding on the chemotherapy regimen after performing molecular testing and determining the tumor mutational burden (TMB) and microsatellite instability (MSI) status [ 28 ].…”

Neoadjuvant Chemotherapy plus Bevacizumab Combined with Total Mesorectal Excision in Treating Locally Advanced Rectal Cancer Patients with BRAF Mutation: Clinical Benefit and Safety

“…Similarly, in a clinical study involving 70 patients with colorectal cancer, it was revealed that the addition of bevacizumab to the NAC produced a good objective response rate, clinical benefit rate, R0 resection rate, and acceptable incidence of adverse reactions. It was indicated that NAC plus bevacizumab is a safe and effective treatment strategy that can improve the life quality of patients [ 25 ].…”

A single-center retrospective analysis of the efficacy and safety of a modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting agents as second-line chemotherapy in Japanese patients with recurrent or nonresectable colorectal cancer

“…The 41 patients collectively received 299 chemotherapy courses. The median number of courses was 6.0 (range, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], corresponding to about 6 months of treatment, and sufficient dose intensity could be obtained (31,32). In about 50% of patients, the duration of a treatment cycle was 5 and not 4 weeks because the off period was 3 rather than 2 weeks (data not shown).…”

“…Accordingly, the treatment regimens FOLFOX4 and FOLFOX6 have frequently been studied in Japanese people because of their smaller body frame ( 18 , 19 ). As we have previously reported, when determining the dose, we aimed to use a minimal chemotherapy dose ( 20 , 21 ). Therefore, at our hospital, we frequently use B-mab-CAPOX (Cape + L-OHP) as the first-line therapy for stage IV recurrent or nonresectable colorectal cancer, and we have reported on the efficacy and safety of this approach ( 20 , 22 , 23 ).…”

“…As we have previously reported, when determining the dose, we aimed to use a minimal chemotherapy dose ( 20 , 21 ). Therefore, at our hospital, we frequently use B-mab-CAPOX (Cape + L-OHP) as the first-line therapy for stage IV recurrent or nonresectable colorectal cancer, and we have reported on the efficacy and safety of this approach ( 20 , 22 , 23 ). For this type of cancer, in January 2015 we introduced a standardized second-line therapy with a modified IRIS regimen, i.e., irinotecan plus S-1 (IRIS) [tegafur/gimeracil/oteracil (S-1)] regimen plus molecular targeting agents (MTA), i.e., the EGFR and VEGF inhibitors B-mab, C-mab, and P-mab.…”