Clinical and pharmacologic effects of combinations of 6-thioguanine and duazomycin A in patients with neoplastic disease.

onists, azaserine (O-diazoacetyl-L-serine) and DON (6diazo-5-oxo-L-norleucine), in combination with either 6mercaptopurine or 6-thioguanine, synergistically inhibit the growth of a spectrum of transplanted neoplasms of rodents ; these results have been summarized in a recent review (20). In man, although the glutarnine analogs have not proved useful, the purinethiols have achieved some importance, and anti-neoplastic activity has been ascribed to 6-mercaptopurine and 6-thioguanine when em ployed alone in the treatment of solid tumors (e.g., Refs. 2, 9, 10, 16). In agreement with the marked anti-neo plastic activity of combinations of azaserine or DON with the purinethiols (20), Schroeder et al. (22, 23) have reported objective responses in 4 out of 7 patients with carcinoma of the breast and in 1 patient with squamous cell carcinoma of the lip who were treated with combina tions of azaserine and 6-thioguanine. Furthermore, in the treatment of acute leukemia, the utilization of com bined therapy with DON and 6-mercaptopurine produced a higher percentage of complete bone marrow remissions than was obtained with the use of 6-mercaptopurine alone (3,4,11,24). The present research was designed to investigate the clinical pharmacology and toxicity of combination therapy