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Clinical and Pharmacologic Effects of Combinations of 6-Thioguanine and Duazomycin A in Patients with Neoplastic Disease¹

Departments of Medicine and Pharmacology, Yale University School of Medicine, New Haven, Connecticut

Nine of 15 patients with solid neoplasms of the head and neck region, treated i.v. with a combination of 6-thioguanine and duazomycin A at daily dosages of 3.0 and 0.6 mg/kg, respectively, showed 50% or greater reduction in the size of tumor masses; toxicity was manifested by leukopenia and thrombocytopenia. The metabolism of 6-thioguanine was studied after both i.v. and p.o. administration of ³⁵S-labeled compound. Sixty-six to 85% of the ³⁵S administered i.v. was excreted in a 24-hr period, whereas only 30–35% of the radioactivity was recovered in the urine of those patients receiving the drug p.o. Analysis of urinary metabolites indicated that thioguanine administered p.o. was degraded to a greater extent than when given i.v. The kinetics of the distribution of urinary metabolites suggested the following catabolic scheme: 6-thioguanine 6-thioxanthine 6-thiouric acid. Concurrent administration of duazomycin A did not significantly affect the metabolic disposition of labeled thioguanine.

¹ This investigation was supported by USPHS research grants CA-02817, CA-5138, CA-05944, and FR-38.

² Burroughs Wellcome Scholar in Clinical Pharmacology.

Received 1/28/65.