Phase I/II trial of dipyridamole, 5-fluorouracil, leukovorin, and mitoxantrone in metastatic breast cancer.
Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m2 by mouth every 6 h (700 mg/m2/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m2 was given intravenously immediately prior to 5-FU 375 mg/m2 intravenously on days 1-5. Mitoxantrone 6 mg/m2 was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m2 days 1-2, 5-FU 375 mg/m2 days 1-2, mitoxantrone 6 mg/m2 on day 2, and dipyridamole 175 mg/m2 every 6 h on days 0-3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.
Budd
G T
GT
Cleveland Clinic Cancer Center, Cleveland Clinic Foundation, OH 44195, USA.
Herzog
P
P
Bukowski
R M
RM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004176:Dipyridamole / Q000008:administration & dosage; D004347:Drug Interactions; D005472:Fluorouracil / Q000008:administration & dosage; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009362:Neoplasm Metastasis
D004176:Dipyridamole; D008942:Mitoxantrone; D002955:Leucovorin; D005472:Fluorouracil