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5-fluorouracil and high dose folinic acid in hormone-refractory metastatic prostate cancer: a phase II study
S D Huan1, S E Aitken, D J Stewart
1Division of Medical Oncology, Ottawa Regional Cancer Centre, Ontario Cancer Treatment & Research Foundation, Canada.
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.
Patients And 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.
Conclusion:
High dose folinic acid did not increase the cytotoxicity of 5-FU in hormone-refractory metastatic prostate cancer.