Clinical and Laboratory Assessment of a Combination of Drugs with Radiation. Coordinated Programme on Improvement in Radiotherapy of Cancer Using Modifiers of Radiosensitivity of Cells. Final Report for the Period 15 March 1976 -

摘要

Applications were clinically studied of misonidazole (MISO) as a hypoxic cell radiosensitizer with pharmacokinetic studies. Work with desmethylmisonidazole was focused on its penetration into the CNS because its low lipophilicity would predict poorer access than MISO. Laboratory work was focused on the interaction of hyperthermia with drugs. Cytotoxicity of MISO induced by hyperthermia was studied. Heat response following hypoxic pretreatment with MISO of EMT6 spheroids showed marked enhancement of subsequent heat killing dependent on the duration of the hypoxic pretreatment. The effect was studied in vitro of preheat temperature at modest temperatures (39 to 43 exp 0 C) on thermal tolerance and subsequent hyperthermic (43 to 44 exp 0 C) interaction with bleomycin, adriamycin and BCNU. Interaction between several cytotoxic drugs and two potentially critical normal tissues, skin and bone marrow was studied in the mouse. No increase in the heat reaction in the skin of the mouse foot was observed following single injections of adriamycin, bleomycin or 5 daily doses of bleomycin together with a single heat treatment. Single doses of BCNU and CTX increased the heat reaction. The radioprotector WR2721 failed to protect against either the heat or heat drug reactions from CTX and BCNU. (Atomindex citation 14:741882)