A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin-refractory metastatic bladder cancer.
BACKGROUND
Bladder cancer is a chemosensitive tumour, however, there is no effective therapy for patients with metastatic disease who failed to respond or relapsed after prior treatment with cisplatin-based chemotherapy. Single agent 5-fluorouracil has modest activity in bladder cancer. The combination of 5-fluorouracil with folinic acid results in stabilization of the ternary complex of 5-fluorodeoxyuridine monophosphate-thymidylate synthetase-5,10 methylene tetrahydrofolate leading to increased DNA inhibition and increased cytotoxicity of 5-fluorouracil.


METHODS
Fourteen evaluable patients with metastatic bladder cancer were treated with 5-fluorouracil at 300 mg/m2 and folinic acid at 200 mg/m2 daily for five days.


RESULTS
There were no complete or partial responses. One patient had a minor response and three patients had stable disease. Diarrhea and mucositis occurred in 25% of patients. There was one treatment-related death.


CONCLUSIONS
High dose folinic acid did not increase the cytotoxicity of 5-fluorouracil in metastatic bladder cancer after cisplatin failure.
Huan
S D
SD
Division of Medical Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
Aitken
S E
SE
Stewart
D J
DJ
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000964:Antimetabolites, Antineoplastic; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil