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), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.
Stöger
H
H
Department of Internal Medicine, Karl Franzens University Graz, Austria.
Bauernhofer
T
T
Schmid
M
M
Ploner
F
F
Moser
R
R
Derstvenscheg
E
E
Steindorfer
P
P
Wilders-Truschnig
M
M
Kuss
I
I
Samonigg
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004317:Doxorubicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use*; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced
D004317:Doxorubicin; C027260:pirarubicin; D002955:Leucovorin; D005472:Fluorouracil