Long duration-mild whole body hyperthermia of up to 12 hours in rats: Feasibility, and efficacy on primary tumour and axillary lymph node metastases of a mammary adenocarcinoma: implications for adjuvant therapy

Abstract

The feasibility and efficacy of low temperature (40°C) long duration whole body hyperthermia (LL-WBH) was investigated in rats bearing a highly metastatic mammary adenocarcinoma (MTLn3). We compared the treatment effects of various durations of LL-WBH (40°C for 2–12 h) to that of conventional short duration-high temperature WBH (SH-WBH, 41.5°C for 2h). SH-WBH, 2h LL-WBH, and 4h LL-WBH resulted in only modest primary tumour growth delays (TGDs) of 0.9, 1.1 and 1.8 d (days) respectively. In contrast, significantly increased TGDs of 2.8, 3.2, 2.6, and 3.1 d were achieved with 6, 8, 10 and 12h LL-WBH, respectively (p < 0.05 compared to SH-WBH, 2h-LL-WBH, and 4h-LL-WBH). Notably, LL-WBH reduced the incidence of axillary lymph node metastasis at 14 days post-treatment, from 100% in normothermic controls and 92% after SH-WBH, to 33, 40, 50, and 60% following 4, 6, 8 and 10h LL-WBH respectively. When the duration of LL-WBH was extended to 12 h, no reduction in axillary lymph node metastasis was observed. Normal tissue toxicity of LL-WBH appeared to be minimal and LL-WBH durations of up to 12h were well tolerated. These data show that LL-WBH for durations of from 4 to 10 h has greater antitumour activity than SH-WBH, against mammary adenocarcinoma, suggesting that LL-WBH may have therapeutic potential in the treatment of malignant disease.