WY 18,251 (Tilomisole), an analog of levamisole: tolerability, and immune modulating effects in cancer patients.
Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a benzimidazole that is structurally similar to the antihelminth levamisole that has recently been approved for the adjuvant treatment of colon cancer. In preclinical models, Tilomisole caused less agranulocytosis than levamisole, but retained immunomodulating capabilities. We examined the effects of Tilomisole administered to cancer patients in four different dose schedules: 60 mg/m2 orally (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients were immunosuppressed when treatment was initiated as defined by standardized assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed lymphocyte responses. Tilomisole was well tolerated with no significant side effects in 25 patients. There were no antitumor responses noted in this setting of metastatic cancer. There was no improvement in concanavalin A or pokeweed mitogen assays at any dose or schedule, but there was sustained improvement in mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily dose. This drug may have favorable biological response modifying effects in vivo and be a suitable alternative to levamisole in cancer treatment, especially if agranulocytosis is a significant problem associated with widespread use of levamisole.
Dillman
R O
RO
Hoag Cancer Center, Newport Beach, CA 92658.
Ryan
K P
KP
Dillman
J B
JB
Shawler
D L
DL
Maguire
R
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004341:Drug Evaluation; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D001562:Benzimidazoles; C029171:tilomisole