Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma.
Fifty patients with locally advanced or metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) at 100 mg orally daily starting on day 1 and cimetidine 300 mg orally four times a day starting on day 15. When disease progressed, coumarin was escalated to 100 mg orally four times a day. Three patients (6%; 95% confidence interval [Cl], 2% to 17%) achieved a partial response, one of those after dose escalation. In addition, one patient had a minor response, then progressing disease, and again had a minor response after dose escalation. All four responders had nonassessable primary tumors (three had had prior nephrectomy and one a renal angioinfarction). The only major toxicity was renal (37 patients had minor to moderate elevations in serum creatinine level). Immunologic studies (hypersensitivity skin testing, lymphocyte blastogenesis response, number of lymphocytes, T lymphocytes, T helper and T suppressor subsets, and T helper: suppressor ratio), performed before and after therapy, showed a relative lymphopenia and decreased hypersensitivity skin-testing results at baseline, and a general decline over time in the number of T cells and T helper and T suppressor subsets. There was no enhancement in any of the immunologic parameters tested. The response rate was 6%, lower than previously reported; a general immunodeficiency was noted at baseline, and the lymphopenia worsened with progressing disease, unaffected by therapy.
Dexeus
F H
FH
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston 77030.
Logothetis
C J
CJ
Sella
A
A
Fitz
K
K
Amato
R
R
Reuben
J M
JM
Dozier
N
N
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary*; D002927:Cimetidine / Q000008:administration & dosage*; D003374:Coumarins / Q000008:administration & dosage*; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D007111:Immunity, Cellular / Q000187:drug effects; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D003374:Coumarins; D002927:Cimetidine; C030123:coumarin