Effects of coumarin (1,2-benzopyrone) and cimetidine on peripheral blood lymphocytes, natural killer cells, and monocytes in patients with advanced malignancies.
The combination of coumarin and cimetidine has yielded objective tumor regressions in patients with metastatic renal cell carcinoma and malignant melanoma. While the mechanism of action of cimetidine appears to be immunomodulatory, coumarin appears to have direct effects on tumor cells as well as immunomodulatory activity. We utilized monoclonal antibody labeling techniques to monitor peripheral blood lymphocyte, natural killer (NK) cell, and monocyte phenotypes in patients treated with coumarin and cimetidine. Patients received coumarin 100 mg orally daily for 14 days; on day 15 cimetidine 300 mg four times daily was added and both drugs were continued until disease progression. Studies were performed pre treatment and at 2, 4, and 8 weeks on therapy. There were no alterations in T-cells, helper/inducer T-cells, cytotoxic/suppressor T-cells, B-cells, Ia + lymphocytes, or NK cells. However, an increase was noted by 2 weeks on therapy in the percentage of monocytes and the percentage of DR+ monocytes. This change in the monocyte population occurred in the presence of coumarin alone, before the institution of cimetidine. While this treatment appears to increase DR expression by monocytes, further studies with larger numbers of patients are needed to determine if this observed change is related to antitumor response.
Marshall
M E
ME
Cell Marker Laboratory, University of Kentucky Medical Center, Lexington 40536-0084.
Riley
L K
LK
Rhoades
J
J
Eichhorn
T
T
Jennings
C D
CD
Cibull
M
M
Thompson
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002927:Cimetidine / Q000627:therapeutic use*; D003374:Coumarins / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*
D003374:Coumarins; D002927:Cimetidine; C030123:coumarin