Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal......

Anticancer Res. 2007 Jul-Aug;27(4C):2605-11.

Significance of thymidine phosphorylase in metronomic chemotherapy using CPT-11 and doxifluridine for advanced colorectal carcinoma.

Ogata Y, Sasatomi T, Mori S, Matono K, Ishibashi N, Akagi Y, Fukushima T, Murakami H, Ushijima M, Shirouzu K.

Department of Surgery, Kurume University School of Medicine, Kurume, 830-0011, Japan. yogata@med.kurume-u.ac.jp

BACKGROUND: A phase II study was designed to evaluate the efficacy, safety and predictors for response of metronomic chemotherapy using weekly low-dosage CPT-11 and doxifluridine (5'-DFUR) in 45 patients with metastatic colorectal cancer.

PATIENTS AND METHODS: Forty mg/m2 of CPT-11 was administered for 3 consecutive weeks in a 4-week treatment cycle, with 5'-DFUR (800 mg/day) given orally.

RESULTS: One or more adverse effects were seen in 42 patients. However, most of these were mild at grade 1 or 2, including only leucopenia in 2, neutropenia in 1, diarrhea in 1 and nausea in 1 as grade 3. The objective response rate was 36% with a median overall survival of 452 days. The response rate in patients with a high expression of thymidine phosphorylase (dThdPase) in tumor cells (47%) was higher (p=0.092) than that (19%) in patients with a low expression.

CONCLUSION: The efficacy of metronomic chemotherapy using low-dosage weekly CPT-1 and 5'-DFUR is worthy of further clinical study, especially in patients with a high expression of dThdPase in primary tumor cells.