The efficacy of long-term oral chemotherapy with 5′-deoxy-5-fluorouridine and cyclophosphamide for recurrent breast cancer

Abstract

Background

5′-Deoxy-5-fluorouridine (5′-DFUR) is a prodrug of 5-fluorouracil (5-FU), which is known to be converted by thymidine phosphorylase (dThdPase). A recent preclinical study revealed that cyclophosphamide (CPA) upregulated dThdPase activity, specifically in tumor cells. The purpose of the present study was to examine the efficacy of long-term administration of 5′-DFUR/CPA for patients with recurrent breast cancer.

Methods

Fifteen breast cancer patients with recurrent tumors entered this study. Ten patients had bone metastasis, five had lung metastasis, and two had liver metastasis. Three patients had multiorgan metastases. All patients had had previous exposure to standard chemotherapy such as CAF (CPA, doxorubicin, and 5-FU) and CMF (CPA, methotrexate, and 5-FU). The patients were orally administered with daily doses of 5′-DFUR at 800–1200 mg and CPA at 200 mg for 2 weeks as induction therapy, followed by 2 weeks’ rest (one to two cycles). Daily doses of 800 mg of 5′-DFUR and 100 mg of CPA (as maintenance therapy) were continuously administered thereafter. Ten of the 15 patients received the maintenance therapy alone. The treatment was continued for at least 24 months (average, 35.2 months).

Results

The main findings included a significant decrease in pain in nine patients with bone metastasis, and this effect continued for more than 2 years. As the pain decreased, the patients’ quality of life (QOL) was improved. Liver metastasis was diminished in two out of two patients. Hematological toxicity of more than grade 3 was recognized in three patients, but only during the induction therapy.

Conclusion

Oral administration of 5′-DFUR/CPA is well tolerated and useful for patients with recurrent breast cancer.