The chemotherapeutic effects of 6-diazo-5-oxo-l-norleucine (DON) and N-[N-γ-glutamyl-6-diazo-5-oxo-norleucinyl]-6-diazo-5-oxo-norleucine (azotomycin) were evaluated in a spectrum of transplantable experimental tumor systems including xenografts of human tumors in athymic mice. Both drugs displayed remarkable activity against the murine leukemia L1210 and P388, the Colon Tumors C26 and C38 and the CD8F1 mammary tumor. No significant activity was observed against Lewis lung carcinoma, B16 melanoma, and intracranial ependymoblastoma. DON and azotomycin also exhibited striking inhibitory effects on the growth of s.c. human tumor (MX-1 mammary, LX-1 lung, and CX-1 and CX-2 colon) xenografts in athymic mice. With the exception of one colon xenograft (CX-1), all tumor lines were markedly responsive to both drugs. Tumor regressions below the initial tumor sizes of 100 to 300 mg, albeit temporary, were brought about by one course of treatment every 4 days for 3 doses (at optimal dose) with either drug. Although these drugs have been tested previously in the clinic and have shown only limited therapeutic effectiveness, they seem to be worthy of a second and closer look in light of the recent laboratory results.
Supported in part by PHS Contracts N01-CM-67099 and N01-CM-57005 from the Drug Evaluation Branch, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute. Part of this report was presented in the Fourteenth Annual Meeting of The American Society of Clinical Oncology, Washington, D. C., April, 1978 (3).