Studies on antitumor effect and intratumor concentrations of thermochemotherapy using cis-diamminedichloroplatinum (II)

Abstract

Thermochemotherapy with cis-diamminedichloroplatinum II (CDDP) was investigated by measurement of the tumor growth curve, histological examination and measurement of intratumor concentrations of CDDP. BALB/c mice with Meth-A fibrosarcomas were used in these studies. Hyperthermia was carried out at 43°C for a 30-minute period using a halogen lamp. Intratumor temperature was measured with a thermistor placed in the center of the tumor.
Tumor growth was delayed after treatment in the animals receiving heat with CDDP and in those receiving heat alone. However, in the animals receiving CDDP alone (5mg/kg intraperitoneal infusion), this effect was not observed. In the animals receiving heat with CDDP, histological examination revealed vacuolation, pyknotic degeneration, and karyorrhexis of tumor cells. With heat alone, the major histological changes to the tumor cells were pyknosis, karyorrhexis, and karyolysis. Therefore, vacuolation can be considered to be a characteristic effect of CDDP administration. Vacuolation was observed earlier in the animals receiving heat with CDDP than in those receiving CDDP alone. We therefore conclude that heating tends to promote the antitumor effect of CDDP. A higher concentration of CDDP was observed from 6 hours to 72 hours after administration in animals receiving heat with CDDP than in those given CDDP alone. When combined with hyperthermia, CDDP tended to remain in the tumor longer than when administered alone.