The Efficacy of Oral Combination Chemotherapy of 5'-DFUR and Cyclophosphamide for Metastatic Breast Cancer

摘要

Purpose A sufficient response rate and good compliance are both important for instituting chemotherapy to treat metastatic breast cancer. Effective oral chemotherapy regimens have long been studied to improve patients' compliance. 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 and especially in tumor cells. The purpose of this study was to examine the efficacy of long-term administration of 5'-DFUR/CPA for the patients suffering with metastatic breast cancer. Methods Thirty four cases with metastatic breast cancer after curative surgery were enrolled in this study. All the patients had been previously exposed to standard chemotherapy such as CMF (CPA, methotrexate, and 5-FU) and CAF (CPA, doxorubicin, and 5-FU). All patients had distant metastasis such as in the bone, lung and liver. Daily treatment consisted of 5'-DFUR 800 mg and CPA 100 mg both were given orally. The treatment was continued for at least 24 weeks. Results The mean age was 49 years and the treatment period ranged from 24 to 60 weeks. The response rate was 35.3%, while it was 26.5% for the patients with stable disease. The mean time to tumor progression was 36 weeks. A significant decrease in pain occurred in twenty patients (69%) with bone metastasis. The frequent adverse effects were leukopenia (32.4%) and gastrointestinal symptoms (20.4%). There was significant correlation between the rate of side effects and the duration of medication ( p =0.010). Conclusion These findings show that oral administration of 5'-DFUR and CPA is well tolerated on an outpatient basis and it was proven to suppress tumor progression. So, an oral combination therapy with 5'-DFUR and CPA may be suitable for metastatic breast cancer.