A phase II study of high-dose cimetidine and the combination 5-fluorouracil, interferon alpha-2A, and leucovorin in advanced renal cell adenocarcinoma.
Cimetidine is an H2-receptor antagonist used in the management of peptic ulcer disease and other hypersecretory gastrointestinal disorders. This agent has intriguing immunomodulatory characteristics. A phase II trial of cimetidine in 19 patients with advanced malignant melanoma yielded an objective response rate of 16%. Having demonstrated that cimetidine is active in malignant melanoma, the authors conducted a phase II trial of cimetidine, 800 mg twice daily by mouth, in patients with advanced renal cell cancer. Among the 31 eligible patients, only one (3.2%) achieved a regression. It was a partial regression lasting 93 days. Median time to treatment failure was 83 days. The combination of interferon alpha-2A (IFL-RA) and 5-fluorouracil (5-FU) has been shown to be synergistic against experimental cell lines in vitro. Citrovorum factor (CF) added to 5-FU has been shown to improve objective tumor response compared with single-agent 5-FU in patients with advanced colorectal cancer. Fluorinated pyrimidines have shown some activity against renal cell cancer. We conducted a phase II trial of the combination of CF at 20 mg/m2 intravenous push followed by 5-FU at 325 mg/m2 intravenously daily for 5 days every week with interferon alpha-2A 5 x 10(6) units/m2 subcutaneously on days 1, 3, 5 in patients with advanced renal cell cancer. Among the 31 eligible patients, only two (6.5%) achieved a regression. Both were partial regressions. Median time to treatment failure was 84 days. Neither regimen is recommended for further testing in patients with advanced renal cell adenocarcinoma.
Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
E T
ET
Creagan
M H
MH
Veeder
V J
VJ
Suman
P A
PA
Burch
W J
WJ
Maples
P L
PL
Schaefer
D M
DM
Pfeifle
R J
RJ
Dalton
A K
AK
Hatfield
M A
MA
Poon
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002927:Cimetidine / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012074:Remission Induction; D016019:Survival Analysis
D006635:Histamine H2 Antagonists; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002927:Cimetidine; D002955:Leucovorin; D005472:Fluorouracil