Yonago Acta medica 1991;34:53-64

Effects of the Timing of Hyperthermia and Chemotherapy on the Antitumor Activity of Thermochemotherapy in vitro and in vivo

Yoshiaki Ikeda

First Department of Surgery, Faculty of Medicine, Tottori University, Yonago 683, Japan

The interval between heating at 42°C for 1 h and treatment with anticancer drugs, cis-diamminedichloroplatinum (II) or mitomycin C, was changed, and effects of the change on in vitro antitumor activity were examined by measuring the 3H-thymidine and 3H-uridine uptakes into mouse ascites hepatoma-134 (MH-134) cells. The uptakes into cancer cells were most effectively inhibited when hyperthermia (HT) and chemotherapy were carried out simultaneously, or when chemotherapy was administered 6 h prior to HT. To study the antitumor effects in vivo of the 2 treatments given at various intervals, MH-134 tumor-bearing C3H/He mice were treated with HT at 43°C for 30 min and chemotherapy at various intervals between the treatments. Tumor growth was most effectively inhibited when the 2 treatments were administered simultaneously. Furthermore, the effects of the timing of treatments on tumor growth in the 2nd round of thermochemotherapy were studied 3 days after the 1st treatment using the animals initially treated with simultaneous HT and chemotherapy. Tumor growth was most effectively inhibited when anticancer drugs were administered 2 h before HT in this case. These experimental results suggest the important factors to be considered with respect to the timing of HT and chemotherapy in clinical thermochemotherapy.

Key words: antitumor activity; in vivo thermochemotherapy; in vitro thermochemotherapy; timing

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