POTENTIATION OF THERAPEUTIC EFFECTS OF 3-[(4-AMINO-2-METHYL-5-PYRIMIDINYL)METHYL]-1-(2-CHLOROETHYL)-1-NITROSOUREA HYDROCHLORIDE BY 6-THIOGUANINE IN MOUSE-TUMOR SYSTEMS - COMPARISON WITH OTHER ANTI-METABOLITES

  • 1 January 1980
    • journal article
    • research article
    • Vol. 71  (1) , 60-72
Abstract
Antitumor activities of a combination chemotherapy with a water-soluble nitrosourea, 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride (ACNU), and a single dose of 6-thioguanine were studied using 3 obstinate murine tumor systems, i.e., Lewis lung carcinoma, B16 melanoma and an advanced stage of L-1210 leukemia systems. A therapeutically synergistic effect was observed either definitely against 1- or 2-day-old Lewis lung carcinoma and 6-day old L-1210 leukemia or moderately against 1-day-old B16 melanoma. Single i.v. treatment on day 7 after s.c. implantation of Lewis lung carcinoma, when the tumors had already metastasized to the lungs, produced a significant regression of tumor and a significant increment in survival time of tumor-bearing mice. The combination of ACNU and 6-thioguanine showed a greater and a wider spectrum of antitumor activities against these tumors than those obtained by the combination with ACNU and a single dose of 5-fluorouracil, methotrexate or 6-mercaptopurine. An increment in lethal toxicity for normal and tumor-bearing mice was not observed by the combination of ACNU and 6-thioguanine in contrast to definite increases in this toxicity by the combination of ACNU and 5-fluorouracil. The clinical utility of the combination chemotherapy with ACNU and 6-thioguanine in the treatment of several solid tumors and acute leukemias is suggested.