© 2007 Foundation for Promotion of Cancer Research
Phase I/II Study of CPT-11 plus UFT in Patients with Advanced/Recurrent Colorectal Cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG): Protocol 0102
1 Department of Surgery, Kansai Rosai Hospital, Amagasaki, Hyogo
2 Third Department of Medicine, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka
3 Department of Surgery, Sakai City Hospital, Sakai, Osaka
4 Second Department of Medicine, Osaka Medical Hospital, Takatsuki, Osaka, Japan
For reprints and all correspondence: Naohiro Tomita, Department of Surgery, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya-city, Hyogo 663-8501, Japan. E-mail: ntomita{at}hyo_med.ac.jp
Received October 17, 2006; accepted February 18, 2007
Objective: The primary objective of this study was to explore the efficacy and safety of combined chemotherapy with CPT-11 and UFT in patients with advanced/metastatic colorectal cancer.
Methods: Twenty-two patients with metastatic colorectal cancer were enrolled in the phase I trial and 35 patients (including eight patients treated at level 4 during phase I) were evaluated in the phase II trial. Treatment consisted of two 35-day cycles of combination chemotherapy with CPT-11 and UFT. During phase I, CPT-11 was administered on days 1 and 15 as an intravenous infusion over 90 min at four different dose levels, starting from a dose of 80 mg/m2 (level 1). During phase II, the dose of CPT-11 was fixed at 150 mg/m2 based on the results of the phase I study. UFT was administered orally at a fixed dose of 300 mg/m2 on days 1–28, followed by a 1-week drug holiday, during each course (35 days).
Results: The maximum tolerated dose (MTD) of CPT-11 was determined to be 150 mg/m2 during the phase I trial. The major toxicities detected during phase II in 35 patients receiving CPT-11 at this recommended dose were grade 3/4 neutropenia in nine patients (25.7%) and grade 3/4 anorexia in six patients (11.4%). No severe adverse events occurred. The overall response rate and the median overall survival time was 22.9% (8/35) and 23.9 months for all patients, respectively. For pre-treated patients they were 26.3% (5/19) and 25.1 months, respectively.
Conclusion: This combination of CPT-11 and UFT is considered to be both feasible and relatively safe. The response rate of the patients receiving CPT-11 at a dose of 150 mg/m2 was comparable to that reported previously for 5-FU-based regimens coupled with CPT-11, and this regimen can probably be beneficial for patients with pre-treated advanced colorectal cancer on an outpatient basis.
Key Words: colorectal cancer • chemotherapy • CPT-11 • UFT • oral fluoropyrimidine