Hamamoto Yasuo, Yamaguchi Tatsuro, Nishina Tomohiro, Yamazaki Kentaro, Ura Takashi, Nakajima Takako, Goto Ayumu, Shimada Ken, Nakayama Norisuke, Sakamoto Junichi, Morita Satoshi, Yamada Yasuhide
Keio Cancer Center, School of Medicine, Keio University, Tokyo, Japan;
Department of Surgery, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan;
Oncologist. 2014 Nov;19(11):1131-2. doi: 10.1634/theoncologist.2014-0159. Epub 2014 Oct 3.
Capecitabine is used mainly with oxaliplatin to treat metastatic colorectal cancer (mCRC). Results from capecitabine plus irinotecan (XELIRI) with or without bevacizumab (BV) have been reported in Europe but not in Japan. Consequently, the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC were assessed in a single-arm phase II study.
Eligible patients had had prior chemotherapy containing BV for mCRC and wild-type or heterozygous UGT1A1. Therapy in each 21-day treatment cycle consisted of capecitabine (800 mg/m(2) twice daily on days 1-15), irinotecan (200 mg/m(2) on day 1), and BV (7.5 mg/kg on day 1). The primary endpoint was dose-limiting toxicity in phase I and progression-free survival (PFS) in phase II.
A total of 34 patients (6 in phase I, 28 in phase II) were enrolled from May 2010 to June 2011. Baseline characteristics included a median age of 60 years (range: 22-74 years) for 24 men and 10 women. No dose-limiting toxicities appeared in phase I. Median PFS was 240 days (95% confidence interval: 179-311 days). Overall response rate was 18.1%, and the disease-control rate was 90.9%. The incidence of adverse events frequently associated with irinotecan and capecitabine were neutropenia (any grade, 55.9%; grade 3 or 4, 11.8%), diarrhea (any grade, 50%; grade 3 or 4, 5.9%), and hand-foot syndrome (any grade, 61.8%; grade 3 or 4, 5.9%).
Our results suggest that XELIRI plus BV is well tolerated and effective as a second-line treatment for mCRC in Japanese patients. This regimen could be especially appropriate for patients resistant to oxaliplatin-based regimens.
卡培他滨主要与奥沙利铂联合用于治疗转移性结直肠癌（mCRC）。卡培他滨联合伊立替康（XELIRI）加或不加贝伐单抗（BV）的研究结果已在欧洲报道，但在日本尚未见报道。因此，在一项单臂II期研究中评估了XELIRI加BV在日本mCRC患者中的安全性和疗效。
符合条件的患者既往接受过含BV的mCRC化疗，且UGT1A1为野生型或杂合型。每21天治疗周期的治疗方案包括卡培他滨（第1 - 15天，800mg/m²，每日2次）、伊立替康（第1天，200mg/m²）和BV（第1天，7.5mg/kg）。主要终点在I期为剂量限制性毒性，在II期为无进展生存期（PFS）。
2010年5月至2011年6月共纳入34例患者（I期6例，II期28例）。基线特征包括24例男性和10例女性，中位年龄60岁（范围：22 - 74岁）。I期未出现剂量限制性毒性。中位PFS为240天（95%置信区间：179 - 311天）。总缓解率为18.1%，疾病控制率为90.9%。与伊立替康和卡培他滨相关的不良事件发生率为中性粒细胞减少（任何级别，55.9%；3或4级，11.8%）、腹泻（任何级别，50%；3或4级，5.9%）和手足综合征（任何级别，61.8%；3或4级，5.9%）。
我们的结果表明，XELIRI加BV耐受性良好，作为日本mCRC患者的二线治疗有效。该方案可能特别适用于对基于奥沙利铂方案耐药的患者。
