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Clinical pharmacology and human antitumor activity of cytosine arabinoside
Author(s) -
Talley Robert W.,
O'Bryan R. M.,
Tucker W. G.,
Loo R. V.
Publication year - 1967
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(1967)20:5<809::aid-cncr2820200536>3.0.co;2-0
Subject(s) - leukopenia , medicine , vomiting , cytosine , nausea , pharmacology , deamination , leukemia , urine , drug , gastroenterology , toxicity , biology , biochemistry , enzyme , dna
Cytosine arabinoside (ara‐C) has been given to 89 patients with various types of neoplastic disease. Hematopoietic toxicity with megaloblastosis, leukopenia, and thrombocytopenia occurred frequently as did nausea and vomiting. Mucosal ulceration and CNS effects were rarely observed. Response in a variety of solid tumors has been disappointing, with only transient decrease in tumor masses being observed in seven of 62 patients treated. Responses in leukemia and lymphosarcoma were more frequent (four of four leukemias and 15 of 23 lymphomas), but these were only partial and of short duration. Experience with several dosage regimens indicated that large doses at seven‐to‐ten day intervals were less toxic and as effective as other regimens in treatment of lymphosarcomas. Biological assay of blood and urine for ara‐C demonstrated disappearance of the drug from the blood within 15 min; only a small proportion appeared in the urine. Other investigators have reported that the major excretion product of ara‐C is uracil arabinoside (ara‐U), due to the presence of pyrimidine deaminases in human liver and kidney tissue. Further investigation of various dosage regimens in treatment of various human malignancies is recommended, as well as a search for agents which will prevent the rapid deamination of ara‐C to ara‐U.