LONG-DURATION, MILD WHOLE-BODY HYPERTHERMIA WITH CISPLATIN - TUMOR RESPONSE AND KINETICS OF APOPTOSIS AND NECROSIS IN A METASTATIC RAT MAMMARY ADENOCARCINOMA

This study examines antitumour effect and induction of apoptosis and n ecrosis after treatment with long-duration, mild whole body hypertherm ia (LL-WBH, 40.O degrees C, for 6 h) in simultaneous combination with cisplatin (CDDP) on primary and metastatic tumour growth in a rat mamm ary adenocarcinoma. A significantly greater delay in primary mammary t umour growth was observed after treatment with LL-WBH + CDDP, compared to either modality alone (p < 0.05). LL-WBH alone caused a significan t delay in spontaneous metastasis to the axillary lymph node (ALN) and LL-WBH + CDDP tended to further increase the delay in ALN metastasis. Survival was longest in rats receiving LL-WBH + CDDP, compared to oth er groups (p < 0.05). CDDP induced a peak of tumour apoptosis at 24 h after treatment beginning that was significantly greater than LL-WBH a lone (p < 0.05). The peak of tumour apoptosis induced by LL-WBH + CDDP from 12 to 24 h was significantly greater than any other group (p < 0 .01). These results suggest that the extent of treatment-induced apopt osis seems to correlate positively with antitumour response and the co mbination of LL-WBH with CDDP may lead to a promising adjuvant therapy for breast cancer.