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Clinical and Pharmacological Studies
8 auth. William, A., Creasey, H., Prusoff, Arnold, ...
The clinical pharmacology of 5-iodo-@'-deoxycytidine (ICDR) has been investigated in twelve patients with advanced neoplastic disorders and compared with that of 5-iodo-@'-deoxyuridine (IUDR). Studies of the catabolism of ICDR-1'@ in four of these p…
The clinical pharmacology of 5-iodo-@'-deoxycytidine (ICDR) has been investigated in twelve patients with advanced neoplastic disorders and compared with that of 5-iodo-@'-deoxyuridine (IUDR). Studies of the catabolism of ICDR-1'@ in four of these patients revealed that be tween 85 and 98 per cent of this compound was deaminated, with subsequent cleavage of the formed IUDR to 5-iodouracil, which, in turn, was de-iodinated, with the forma tion of iodide. Objective evidence of inhibitory effects on various rapidly growing normal tissues was noted after treatment with ICDR and included stomatitis, hair loss, nail changes, and hematopoietic depression similar to that observed after administration of IUDR. In those patients in whom metabolic studies with ICDR-I'@ were performed, and in whom an adequate maintenance of blood levels of IUDR-I'25 did not occur, typical signs of toxicity were not seen, and significant antineoplastic effects were not produced. In one patient in whom sustained blood levels of IUDR-I'@ resulted from the ICDR-I'25 injected, a marked regression of a carcinoma of the vulva was obtained repeatedly on four occasions. Both the antineoplastic effects and the manifestations of toxicity ob served in this patient were comparable to those seen after an identical course of therapy with IUDR-I'@.
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1 | 2006 |
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