Enhancement of radioresponse of a mouse mammary carcinoma to combined treatments with hyperthermia and radiosensitizer misonidazole.

The regrowth delay of a transplanted syngeneic mouse mammary carcinoma designated MT2 was used to estimate the effects of three-fold combination treatments: X-irradiation; hyperthermia and radiosensitizer; and misonidazole (Ro-07-0582). The experiment entailed five groups of experimental mice: untreated control; X-rays alone; X-rays plus hyperthermia (42--43 degrees); X-rays plus misonidazole; and X-rays plus hyperthermia plus misonidazole. X-Ray treatments consisted of 4000 rads administered locally to the tumors in two equal fractions at a 48-hr interval. Misonidazole (0.67 mg per g body weight) was injected i.p. 30 min before exposure to X-irradiation. Hyperthermia was administered 10 min prior to and for 17 min during irradiation. The regrowth delay factor of 3.9 was obtained by administering combined treatments of the three agents (X-rays plus hyperthermia plus misonidazole). The enhancing effect on a syngeneic mouse mammary adenocarcinoma by the modality of treatment herein described lends support to the usefulness of combining X-rays with other agents in the treatment of neoplasms.