A single-arm phase II trial of combined chemotherapy with S-1, oral leucovorin, and bevacizumab in heavily pre-treated patients with metastatic colorectal cancer

BMC Cancer

Research Article

Masashi Andoh¹  Shigenori Kadowaki¹  Hiroya Taniguchi¹  Takashi Ura¹  Kei Muro¹  Yukiya Narita¹  Daisuke Takahari¹  Azusa Komori¹  Motoo Nomura¹  Sohei Nitta¹  Kazuhisa Yamaguchi²  Keita Mori³  Yoshinori Igarashi⁴ 

[1] Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, 464-8681, Nagoya, Aichi, Japan;Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, 464-8681, Nagoya, Aichi, Japan;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, 6-11-1 Omorinishi, 143-8541, Ota-ku, Tokyo, Japan;Division of Clinical Research Promotion Office, Depertment of Clinical, Research Support Center, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi–cho, 411-8777, Sunto-gun, Shizuoka, Japan;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, 6-11-1 Omorinishi, 143-8541, Ota-ku, Tokyo, Japan;

关键词: Metastatic colorectal cancer;    S-1;    Bevacizumab;    Leucovorin;    KRAS;    BRAF;    Chemotherapy;   

DOI  :  10.1186/s12885-015-1606-1

 received in 2014-12-25, accepted in 2015-08-18,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe mean 5–6-month survival after failed standard chemotherapy for metastatic colorectal cancer (mCRC) necessitates more effective treatments for refractory mCRC. For untreated mCRC, S-1 + oral leucovorin (SL) therapy offers promising results without severe toxicity. The ML18147 trial demonstrated that bevacizumab (Bev) prolongs overall survival after mCRC progression. We conducted a single-centre phase-II trial to evaluate the safety and efficacy of SL/Bev combination chemotherapy as mCRC salvage therapy.MethodsMajor eligibility criteria were confirmed adenocarcinoma diagnosis; age >20 years; Eastern Cooperative Oncology Group performance status, 0–2; and progression after administration/intolerance of/to approved drugs for mCRC. (5-FU, oxaliplatin, irinotecan, Bev, and anti-EGFR antibody, if KRAS wild-type). S-1 (80–120 mg/body) and leucovorin (25 mg) were orally administered in a 1-week-on/1-week-off schedule. Bev (5 mg/kg) was administered on day 1 of every 2-week cycle. The primary endpoint was disease control rate (DCR).ResultsA total of 31 patients were enrolled. DCR was 65 % [95 % confidence interval (CI), 48–100 %] and the response rate was 7 % (95 % CI, 0.7–22 %). One patient showing partial response to SL/Bev had a BRAF-mutant tumor. Median progression-free survival and overall survivals were 5.3 [95 % CI, 2.1–9.3] and 9.9 [95 % CI, 7.4–NA] months, respectively. The most-frequent grade-3/4 adverse events were mucositis (26 %) and diarrhea (11 %), which were manageable by dose reduction/interruption.ConclusionsSL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC.Trial registrationThis study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry (IDUMIN000009083) on 11 October 2012.

【 授权许可】

CC BY   
© Yamaguchi et al. 2015