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Blood Flow-interrupting Hyperthermic Chemotherapy on Established Autochthonous Mouse Sarcoma Induced by 3-Methylcholanthrene¹

Department of Cell Research, Cancer Research Institute, Faculty of Medicine, Kyushu University, Fukuoka, Japan 812

Established autochthonous sarcomas induced in the hind limbs of mice by 3-methylcholanthrene were treated with our method of "regional blood flow-interrupting hyperthermic chemotherapy."

After administration of an injection of 20% of the dose of carbazilquinone (CQ) lethal for 50% of the animals (1 mg/kg i.v.), followed by temporary interruption of blood flow of the tumor-bearing limbs and warming of the limbs at 37° for 60 min, we found that the tumor-bearing mice survived significantly (p < 0.001) longer than did the control mice treated with CQ injection alone. One of 23 mice treated thusly (4.3%) survived without any tumor growth for 24 weeks, and the animal walked with an almost normal gait, using the treated limb. With injection of 12.5% of the dose of CQ lethal for 50% of the animals (0.62 mg/kg), warming of the region for 30 min at 41° was more effective than was warming for 60 min at 37° in the present chemotherapeutic system. The side effects on regional normal tissues, induced by the treatments, were almost the same between the two chemotherapeutic conditions.

Nitrogen mustard N-oxide and mitomycin C were also tested for comparison in the same experimental system. Nitrogen mustard N-oxide revealed remarkable antitumor effects, but its side effects on regional normal tissues were more severe than were those of CQ. Mitomycin C showed fewer antitumor effects than did CQ.

¹ Supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by the Princess Takamatsu Cancer Research Fund.

Received 6/22/77. Accepted 12/ 2/77.