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

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.

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.

CONCLUSIONS

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.