Sensitization by SR-2508 plus Ro 03-8799.
The primary toxicity of Ro 03-8799 is a central nervous system toxicity, whereas that of SR-2508 is a peripheral neuropathy. The feasibility of reducing overall toxicity while maintaining maximal radiosensitization by using the two sensitizers together was tested. The LD50/2 of Ro 03-8799 was 0.68 mg/g body wt (mg/gbw) after intravenous (i.v.) administration, and that of SR-2508 was 4.4 mg/gbw after i.v. administration. When both drugs were given together in equitoxic proportions, the LD50/2 was 0.45 mg of Ro 03-8799 plus 2.9 mg of SR-2508/gbw. These doses are 66% of the respective LD50/2 values of the drugs when given separately. Radiosensitization was evaluated using in vivo-in vitro assays with EMT6/SF tumors in BALB/c mice. At drug doses between 10 and 60% of the LD50/2, sensitization was generally maximal and similar to that from misonidazole, but there was less sensitization below this dose, both with the drugs given separately and together. If chronic toxicities of these drugs overlap as do the acute toxicities there will be little or no additional benefit from using these drugs in combination, compared to using them separately.
D000818:Animals; D003131:Combined Modality Therapy; D004338:Drug Combinations; D017341:Etanidazole; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy*; D009593:Nitroimidazoles / Q000627:therapeutic use* / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use* / Q000633:toxicity
D004338:Drug Combinations; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; C033815:pimonidazole