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