A phase I study of oral UFT/leucovorin and irinotecan, plus radiation for locally recurrent rectal cancer


Masataka Ikeda1), Mitsugu Sekimoto1), Yosuke Fukunaga2), Koji Konishi3), Yushi Fujiwara4), Tsunekazu Mizushima5), Ichiro Takemasa5), Hirofumi Yamamoto5), Yuichiro Doki5), Masaki Mori5)

1) Department of Surgery, Osaka National Hospital, Osaka, Japan
2) Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan
3) Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
4) Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
5) Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Japan


Objectives: 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. Methods: Patients with histologically proven rectal cancer with local recurrence were eligible for this study. Escalating doses of CPT-11 (30-60 mg/m2) were administered on days 3, 10, 24, and 31. UFT (300 mg/m2) 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. Results: We recruited 27 patients, and the MTD of CPT-11 was 60 mg/m2 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. Conclusions: 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/m2 of CPT-11.

Released: April 28, 2017; doi: dx.doi.org/10.23922/jarc.2016-009