Combination therapy by trastuzumab with 5'-deoxy-5-fluorouridine and cyclophosphamide in patients with metastatic breast cancer.

BACKGROUND: Trastuzumab (Herceptin®) was clinically introduced in Japan in 2001 to treat metastatic breast cancer patients who show an over-expression of human epidermal growth factor receptor 2 (HER2). Since that time, this anticancer drug has played an important role in the treatment of cancer. In the present retrospective study, trastuzumab was administered in combination with 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPM) as the third- to sixth- line therapy in 25 patients whose HER2-positive metastatic breast cancers did not respond but showed recurrence after treatment with several chemotherapeutic regimens, namely, trastuzumab alone, and trastuzumab combined with taxane or other anticancer drugs.

METHODS: Trastuzumab was administered at a dose of 2 mg/kg (at a loading dose of 4 mg/kg) once weekly; 5'-DFUR, at an oral daily dose of 800-1200 mg/body; and CPM, at an oral daily dose of 100 mg/body for 2 weeks followed by one week discontinuation of the drug.

RESULTS: The response rate to the combination therapy was 32% (95% confidence interval, 17-52%). Grade 3 adverse effects, according to National Cancer Institute-Clinical Therapeutic Conference version 2.0. (NCI-CTC ver. 2.0), included: neutropenia in 7 patients, anemia in one, and elevation of alkaline phosphatase (ALP) in one. Other adverse events of grade 1 or 2 in accordance with NCI-CTC included general fatigue, nausea, vomiting, thrombocytopenia, increased transaminase, and decreased serum albumin. All adverse events were easily controllable and reversible after discontinuation of the drug.

CONCLUSIONS: Combination therapy with trastuzumab, 5'-DFUR and CPM is effective and well tolerated as the third- to six line treatment option for patients with HER2-overexpressing metastatic breast cancer.

MINI-ABSTRACT: Combination therapy by trastuzumab with 5'-DFUR and cyclophosphamide can be safely administered on an outpatient basis and is useful to treat patients with HER2-overexpressing metastatic breast cancer.