Experimental Studies on timing of drug administration in thermochemotherapy through CDDP.
We investigated the optimum timing of cis-diamminedichloroplatinum (II) (CDDP) administration in thermochemotherapy. BALB/c mice with Meth-A fibrosarcoma were used in this study. Hyperthermia was carried out at 43°C for a 30 minutes using a halogen lamp, and the intratumor temperature was measured with a thermistor placed in the center of the tumor. Simultaneously intratumor blood flow was measured by Laser Doppler flowmetry. Intratumor concentration of CDDP was determined by atomic absorption spectrometry. CDDP (5mg/kg) was administered intraperitoneally at the following 6 times in relation to heating: immediately before or after heating, 3 hours before or after, heating and 6 hours before or after heating. Hyperthermia only was performed in a control group and CDDP treatment only group was also investigated.
Results:
1. The influence of the timing of CDDP administration on antitumor effect.
When CDDP was administered just before or after heating, as well as 3 hours before heating, delay of marked growth of the tumor was observed.
2.The intratumor blood flow continued to decrease immediately after heating until 24 hours later.
3.The relationship between intratumor concentration and the timing of CDDP administration.
When CDDP was administered just before heating, the highest intratumor concentration of CDDP was observed and CDDP concentrations were lower in the other groups. When combined with heating, CDDP tended to remain in the tumor tissue at a lower concentration for a longer period than when it was administered alone.
4.The relationship between intratumor concentration and antitumor effect, and conclusion.
It was found that a high concentration of CDDP was not always associated with a greater effect. In conclusion, for thermochemotherapy using CDDP, it seemed to be important for CDDP administration and heating to be performed as close as possible in order to achieve a good antitumor effect.
