ABSTRACT
BACKGROUND: Chemotherapy is most effective when applied during the biologically active stage of tumor cells. According to the authors' previous tumor marker kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect in an MF-resistant population. In the latter, the suppressive effect was transient and the biologic activity resumed in one week after MF administration. METHODS: Based on this marker kinetic study, an alternating chemotherapy program was designed to study its antitumor and side effects. Methotrexate (M) (200 mg/m2) and 5-fluorouracil (F) (500 mg/m2) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m2 orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m2), doxorubicin (A) (50 mg/m2), and vincristine (V) (1 mg/m2) were given on day 8. The MFL/CAV was given every 4 weeks. RESULTS: Forty-nine patients with metastatic breast cancer were enrolled; 41 were eligible. There were 5 complete and 23 partial remissions, producing a total response rate of 68%. In 15 patients with liver metastases, the response rate was 73% and the median survival 13.7 months, results superior to those previously reported for this subgroup of patients. Side effects were manageable. CONCLUSIONS: This regimen, which can be given safely in an outpatient setting, yielded encouraging response and survival rates in patients with visceral-dominant disease with poor prognoses.
