A PHASE-I II STUDY OF 4'-O-TETRAHYDROPYRANYL-DOXORUBICIN, 5-FLUOROURACIL, AND HIGH-DOSE LEUCOVORIN AS FIRST-LINE THERAPY IN ADVANCED BREAST-CANCER PATIENTS/

A total of 50 patients were treated weekly with 5-fluorouracil (FU), l eucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first- line chemotherapy for advanced breast cancer (ABC). In phase I the dos es of LV (500 mg/m(2), day 1) and FU (350 mg/m(2), day 1) were held co nstant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m(2) up to the maximum tolerated dose (MTD). Twenty-eigh t patients entered phase I, and MTD for THP was defined as 35 mg/m(2) in this combination. Dose-limiting toxicities were myelosuppression an d hepatotoxicity. In phase II, another 22 patients were treated with T HP at a dose level of 30 mg/m(2). Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for respon se: I patient obtained a complete response (CR) and 13 showed a partia l response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survi val, 15.5+ month s. Side effects were generally mild, with ECOG grade I and II leukopen ia in 51% of all cycles and grade III in 3% of the courses. Other toxi city included nausea and vomiting (54% and 8%, respectively) and alope cia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line trea tment of ABC with relative low toxicity.