In vivo combination of misonidazole and the chemotherapeutic agent CCNU.
The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D008130:Lomustine / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D008920:Misonidazole / Q000627:therapeutic use* / Q000633:toxicity; D009593:Nitroimidazoles / Q000627:therapeutic use*; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D009593:Nitroimidazoles; D009607:Nitrosourea Compounds; D008130:Lomustine; D008920:Misonidazole