5-fluorouracil and high dose folinic acid in hormone-refractory metastatic prostate cancer: a phase II study.
BACKGROUND
The response of hormone-refractory metastatic prostate cancer to chemotherapy is poor. The antitumour activity of single agent 5-fluorouracil (5-FU) is approximately 15%. Folinic acid is a reduced folate which when combined with 5-FU augments the activity of 5-FU by stabilizing the ternary complex of 5-deoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate, resulting in increased DNA inhibition and in increased cytotoxicity of 5-FU.


METHODS
We used the combination of 5-FU at 300-370 mg/m2 and folinic acid at 200 mg/m2 daily for five days in 16 patients with hormone-refractory metastatic prostate cancer.


RESULTS
A total of 15 evaluable patients were treated. There were no complete or partial responses. Seven patients had stable disease. Diarrhea constituted the most common non-hematologic toxicities (67%). Four patients experienced grade 3 and 4 neutrophil toxicity. There was one treatment-related death from an acute enterocolitis and peritonitis in a patient with grade 4 neutropenia.


CONCLUSIONS
High dose folinic acid did not increase the cytotoxicity of 5-FU in hormone-refractory metastatic prostate cancer.
Huan
S D
SD
Division of Medical Oncology, Ottawa Regional Cancer Centre, Ontario Cancer Treatment & Research Foundation, Canada.
Aitken
S E
SE
Stewart
D J
DJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D002955:Leucovorin; D005472:Fluorouracil