Synthesis and antitumour activity of 4-nitroso-4-(2-chloroethyl)semicarbazides.

1-Methyl-1-(2-chloroethyl)-4-nitroso-4-(2-chloroethyl)semicarbazide, 1,1-di-(2-chloroethyl)-4-nitroso-4-(2-chloroethyl)semicarbazide and 1,1-di-(2-bromoethyl)-4-nitroso-4-(2-chloroethyl)semicarbazide, which are a novel class of nitrosoureas containing hydrazinomustard residue, have been synthesized. A dose-dependent antitumour activity was found with the three tested compounds.

Chemo- and immunotherapy of an adenovirus-induced transplantable sarcoma in hamsters.

The subcutaneous transplantable adenovirus sarcoma (TAVS) in hamsters was created in 1972 at the Oncological Research Institute and maintained by serial subcutaneous transplantation. It showed the highest sensitivity against some alkylating drugs and antimetabolites--cyclophosphamide, sarcolysine, methotrexate and 6-mercaptopurine. In some degree, TAVS is able to differentiate antitumor drugs of one group by the intensity of their antitumor activity. Among the drugs, cyclophosphamide was the most active and 6-mercaptopurine and 5-fluorouracil the least active. Antitumor drugs of plant origin, antibiotics and methyl-CCNU had a weak activity on subcutaneous TAVS. Intramuscular TAVS showed a similar sensitivity, with some differences for olivomycin, bruneomycin and vinblastine. Intracerebral TAVS was sensitive against antitumor agents penetrating through the hemato-encephalic barrier and which were active against its subcutaneous and intramuscular form. BCG vaccine and levamisole applied separately did not show any activity on the growth of TAVS. Combined immunochemotherapy with cyclophosphamide plus BCG gave a better enhancement of the antitumor effect of the cytostatic than that of the combination of methotrexate plus BCG and cyclophosphamide plus levamisole. These results showed that TAVS in hamsters may be used as a suitable experimental model for pharmacological studies of antitumor agents and combined immunochemotherapy.