Ikeda Masataka, Sekimoto Mitsugu, Fukunaga Yosuke, Konishi Koji, Fujiwara Yushi, Mizushima Tsunekazu, Takemasa Ichiro, Yamamoto Hirofumi, Doki Yuichiro, Mori Masaki
Department of Surgery, Osaka National Hospital, Osaka, Japan.
Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan.
J Anus Rectum Colon. 2018 May 25;1(2):50-55. doi: 10.23922/jarc.2016-009. eCollection 2017.
The aim of this phase I study is to identify the maximum tolerated dose (MTD) and recommended dose (RD) of CPT-11 in combination with UFT/LV and radiation in patients with locally recurrent rectal cancer.
Patients with histologically proven rectal cancer with local recurrence were eligible for this study. Escalating doses of CPT-11 (30-60 mg/m) were administered on days 3, 10, 24, and 31. UFT (300 mg/m) and LV (75 mg/body) were given on days 1-5, 8-12, 22-26, and 29-33. Radiotherapy doses consisted of 50 Gy in daily fractions of 2.0 Gy each, 5 times per week, for total 5 weeks.
We recruited 27 patients, and the MTD of CPT-11 was 60 mg/m due to the occurrence of dose-limiting toxicity of grade 3 diarrhea. Major grade 3 adverse events were neutropenia (5/27; 18.5%) and diarrhea (6/27; 22.2%). No grade 4 adverse event was observed throughout this treatment.
The combined chemoradiotherapy with oral UFT/LV plus CPT-11 is feasible and promising. The recommended dose for further phase II trials is determined to be 50 mg/m of CPT-11.
本I期研究旨在确定伊立替康（CPT-11）联合优福定/亚叶酸钙（UFT/LV）及放疗用于局部复发性直肠癌患者时的最大耐受剂量（MTD）和推荐剂量（RD）。
经组织学证实为局部复发性直肠癌的患者符合本研究条件。在第3、10、24和31天给予递增剂量的CPT-11（30 - 60 mg/m²）。在第1 - 5、8 - 12、22 - 26和29 - 33天给予优福定（300 mg/m²）和亚叶酸钙（75 mg/体）。放疗剂量为50 Gy，每天2.0 Gy，每周5次，共5周。
我们招募了27例患者，由于发生3级腹泻的剂量限制性毒性，CPT-11的MTD为60 mg/m²。主要的3级不良事件为中性粒细胞减少（5/27；18.5%）和腹泻（6/27；22.2%）。在整个治疗过程中未观察到4级不良事件。
口服优福定/亚叶酸钙联合CPT-11的同步放化疗是可行且有前景的。确定进一步II期试验的推荐剂量为CPT-11 50 mg/m²。
