Combining anti-tumor drugs with mild hyperthermia increases the cytotoxic effects of drugs on human leukemia cells in vitro

Although the benefits of using a combination of hyperthermia and chemotherapy or radiotherapy in the treatment of cancer have been theoretically established, the use of such combination therapy is not widespread at the clinical level, as the application of hyperthermia is complex and maintaining a tumor temperature of 43°C or higher is exceedingly difficult. Consequently, in the present study, the effects of chemotherapy combined with mild hyperthermia at 41°C (which is easier to apply than standard hyperthermia) were examined in the NALM-6 leukemia cell line. The results were as follows: i) NALM-6 leukemia cells, like most cells, survived mild hyperthermia at 41°C, but were killed at temperatures over 43°C. ii) Low concentrations of adriamycin (0.1 µg/ml) or mild hyperthermia applied separately did not have a visible effect on the survival rate of NALM-6 cells, whereas combined treatment with these therapies decreased the survival rate of NALM-6 cells in a time-dependent manner. The anti-tumor effect after 5 h of the combination of 0.1 µg/ml adriamycin and mild hyperthermia was the same as that observed with a 10-fold higher concentration (1 µg/ml) of adriamycin alone. iii) Another anti-tumor drug, vincristine, exhibited the same behavior as adriamycin. The anti-tumor effect after 1 h of the combination of 5x10−11 M vincristine and mild hyperthermia was the same as that observed with a 10-fold higher concentration (5x10−10 M) of vincristine alone. The results indicate that it may be possible to reduce the required concentrations of anti-tumor drugs by using them in combination with mild hyperthermia. In this way, the side effects of chemotherapy may be reduced in clinical settings. Mild hyperthermia is a useful and practical heating method, and could result in the increasing clinical application of hyperthermia in the treatment of cancer.