ALTERNATING CHEMOTHERAPY REGIMENS FOR PATIENTS WITH METASTATIC BREAST-CANCER - A PILOT-STUDY BASED ON TUMOR-MARKER KINETICS

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/m(2)) and 5-fluorouracil (F) (500 mg/m(2)) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m(2) orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m(2)), doxorubicin (A) (50 mg/m(2)), and vincristine (V) (1 mg/m(2)) 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.