Yoshida Yoichiro, Yamada Takeshi, Matsuoka Hiroshi, Sonoda Hiromichi, Fukazawa Atsuko, Yoshida Hiroshi, Ishida Hideyuki, Hirata Keiji, Hasegawa Suguru, Sakamoto Kazuhiro, Otsuka Toshiaki, Koda Keiji
Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
J Anus Rectum Colon. 2019 Jul 30;3(3):136-141. doi: 10.23922/jarc.2018-043. eCollection 2019.
Treatment with TAS-102 has significantly improved the progression-free survival (PFS) and overall survival (OS) of patients with metastatic colorectal cancer (mCRC). Reportedly, the combination of TAS-102 plus bevacizumab extends the median PFS. The present study aimed to confirm the efficacy and safety of TAS-102 plus bevacizumab (biweekly administration) as third-line chemotherapy for patients with mCRC.
METHODS/DESIGN: This is a single-arm, open-label, prospective, nonrandomized, multicenter phase II trial conducted in Japan. With a threshold and expected PFS of 2.1 and 3.5 months, respectively, the simulation results showed a sample size of 42 with α = 0.05 (both sides) for 90% power, based on the One-Arm Binomial test using the SWOG statistical tool. If the estimated dropout is 7%-8%, the target sample size is estimated to be 45. The TAS-CC4 study regimen comprised 28-day cycles with biweekly oral administration of TAS-102 (35 mg/m twice daily on days 1-5 and 15-19 of every 28-day cycle) and bevacizumab (5.0 mg/kg on days 1 and 15). The primary end point is the PFS; secondary end points include response rate (RR), OS, grade ≥3 neutropenia, and genetic alterations (KRAS/BRAF mutations) in the circulating cell-free DNA.
The present study can contribute to the determination of the effective dosing interval of TAS-102 and bevacizumab in patients with mCRC and is thought to lead to prophylaxis of neutropenia and prolongation of the treatment period.
TAS-102治疗已显著改善转移性结直肠癌（mCRC）患者的无进展生存期（PFS）和总生存期（OS）。据报道，TAS-102联合贝伐单抗可延长中位PFS。本研究旨在证实TAS-102联合贝伐单抗（每两周给药一次）作为mCRC患者三线化疗的疗效和安全性。
方法/设计：这是一项在日本进行的单臂、开放标签、前瞻性、非随机、多中心II期试验。基于使用SWOG统计工具的单臂二项式检验，模拟结果显示，阈值和预期PFS分别为2.1个月和3.5个月时，样本量为42，α = 0.05（双侧），检验效能为90%。如果估计的失访率为7%-8%，则目标样本量估计为45。TAS-CC4研究方案包括28天周期，每两周口服一次TAS-102（每28天周期的第1-5天和第15-19天，每日两次，每次35 mg/m²）和贝伐单抗（第1天和第15天，5.0 mg/kg）。主要终点是PFS；次要终点包括缓解率（RR）、OS、≥3级中性粒细胞减少以及循环游离DNA中的基因改变（KRAS/BRAF突变）。
本研究有助于确定mCRC患者中TAS-102和贝伐单抗的有效给药间隔，并且被认为可预防中性粒细胞减少并延长治疗期。
