Yamaguchi Kazuhisa, Taniguchi Hiroya, Komori Azusa, Narita Yukiya, Nitta Sohei, Nomura Motoo, Kadowaki Shigenori, Takahari Daisuke, Ura Takashi, Andoh Masashi, Muro Kei, Mori Keita, Igarashi Yoshinori
Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Aichi, Japan.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Omori Medical Center, 6-11-1 Omorinishi, Ota-ku, 143-8541, Tokyo, Japan.
BMC Cancer. 2015 Aug 27;15:601. doi: 10.1186/s12885-015-1606-1.
The 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.
Major 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).
A 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.
SL/Bev showed impressive activity in refractory mCRC and was tolerable, suggesting its potential as an alternative chemotherapy for refractory mCRC.
This study has been registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry ( ID UMIN000009083 ) on 11 October 2012.
转移性结直肠癌（mCRC）标准化疗失败后的平均5 - 6个月生存期，使得需要更有效的难治性mCRC治疗方法。对于未经治疗的mCRC，S-1联合口服亚叶酸钙（SL）疗法可提供有前景的结果且无严重毒性。ML18147试验表明，贝伐单抗（Bev）可延长mCRC进展后的总生存期。我们进行了一项单中心II期试验，以评估SL/Bev联合化疗作为mCRC挽救疗法的安全性和疗效。
主要入选标准为确诊腺癌；年龄>20岁；东部肿瘤协作组体能状态为0 - 2；以及在给予mCRC批准药物后出现进展/不耐受（如果KRAS野生型，则为5-氟尿嘧啶、奥沙利铂、伊立替康、Bev和抗表皮生长因子受体抗体）。S-1（80 - 120 mg/体）和亚叶酸钙（25 mg）按1周用药/1周停药方案口服给药。Bev（5 mg/kg）在每2周周期的第1天给药。主要终点为疾病控制率（DCR）。
共纳入31例患者。DCR为65%[95%置信区间（CI），48 - 100%]，缓解率为7%（95% CI，0.7 - 22%）。1例对SL/Bev表现出部分缓解的患者肿瘤为BRAF突变型。中位无进展生存期和总生存期分别为5.3[95% CI，2.1 - 9.3]和9.9[95% CI，7.4 - 无可用值]个月。最常见的3/4级不良事件为粘膜炎（26%）和腹泻（11%），可通过剂量减少/中断来控制。
SL/Bev在难治性mCRC中显示出令人印象深刻的活性且耐受性良好，表明其作为难治性mCRC替代化疗的潜力。
本研究于2012年10月11日在大学医院医学信息网络（UMIN）临床试验注册中心注册（编号UMIN000009083）。
