Antineoplastic efficacy of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine, in combination with diazoxide or insulin in autochthonous mammary carcinoma of the Sprague-Dawley rat.
The anticancer activity of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine (CNC-omega-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-omega-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-omega-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (less than 20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.
Klenner
T
T
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Berger
M R
MR
Zelezny
O
O
Fink
M
M
Schmähl
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003981:Diazoxide / Q000008:administration & dosage*; D005260:Female; D007328:Insulin / Q000008:administration & dosage*; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D007328:Insulin; D009607:Nitrosourea Compounds; C063435:N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine; D008239:Lysine; D003981:Diazoxide; D008558:Melphalan