A Phase I/II Trial of TS-1 and Oxaliplatin in Patients With Advanced Colorectal Cancer
Summary
Capecitabine and oxaliplatin(XELOX) is active first-line therapy for patients with metastatic colorectal cancer. Phase II study of TS-1, a novel oral fluoropyrimidine derivative, showed activity in patients with metastatic colorectal carcinoma. Preclinical data of TS-1 with oxaliplatin showed synergistic activity in vivo human colorectal cancer xenograft. There is no data about the optimal dose of TS-1 with 2 weeks schedule combined with oxaliplatin. Therefore in a phase I study, we would like to determine the maximum tolerated dose(MTD) of TS-1 and oxaliplatin and define the recommended dose for subsequent phase II study. And then, in a phase II study we would like to evaluate the efficacy(response rates) and toxicities of the new combination regimen in advanced colorectal cancer.
Timeline
- Start
- 2006-08
- Primary completion
- 2008-06
- Completion
- 2009-03
Publications
- Background Naktsuka M, Saito H, et al., A new combination chemotherapy based on oral fluoropyrimidine, TS-1 combined with oxaliplatin is highly effective against colorectal cancer in vivo 97th AACR Annual Meeting, #4730, 2006
- Results Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, Debraud F, Figer A, Grossmann J, Sawada N, Schoffski P, Sobrero A, Van Cutsem E, Diaz-Rubio E. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004 Jun 1;22(11):2084-91. doi: 10.1200/JCO.2004.11.069.
- Results Shirao K, Ohtsu A, Takada H, Mitachi Y, Hirakawa K, Horikoshi N, Okamura T, Hirata K, Saitoh S, Isomoto H, Satoh A. Phase II study of oral S-1 for treatment of metastatic colorectal carcinoma. Cancer. 2004 Jun 1;100(11):2355-61. doi: 10.1002/cncr.20277.
- Results Emura T, Suzuki N, Yamaguchi M, Ohshimo H, Fukushima M. A novel combination antimetabolite, TAS-102, exhibits antitumor activity in FU-resistant human cancer cells through a mechanism involving FTD incorporation in DNA. Int J Oncol. 2004 Sep;25(3):571-8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Oxaliplatin | Small molecule | 130 mg/m2 | Intravenous |
| Subject | S-1 | Small molecule | 60 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 70 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 80 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 90 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 100 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 110 mg/m2 | Oral |
| Subject | S-1 | Small molecule | 120 mg/m2 | Oral |