Although the combined use of cytotoxic agents and radiation therapy has given promising results in selected human tumors, increased injury to normal tissues produced by the combined regimen has been a major limiting factor. Vitamin A and synthetic retinoids have been shown to modulate the growth and differentiation of normal, premalignant, and malignant cells in vitro and in vivo. More recently, the combined use of retinoic acid and interferon alpha has been shown to be an effective regimen for locally advanced squamous cell carcinoma of the skin and cervix. Based upon preclinical and clinical data, we carried out cell culture studies to determine the effectiveness of a combination regimen of retinoic acid and interferon alpha plus radiotherapy. The results of cell culture studies using human tumor cells show there is a substantial synergistic effect with a combination regimen consisting of retinoic acid, interferon, and radiation therapy.
Synergism is highly dependent on the time and sequence of the combined regimen.
A combination of radiation therapy and hyperthermia has been shown to increase the tumor control probability in the treatment of locally advanced superficial cancers of malignant melanoma, breast cancer, and head and neck tumors. In an effort to selectively enhance the efficacy of hyperthermia with the use of chemical agents, we investigated the use of vitamin K3, menadione. Energy deprivation of cancer cells increases sensitivity to killing by hyperthermia. Since menadione has anti-tumor activity by interfering with the energy metabolism of cells, we studied the cytotoxic effects of menadione in combination with mild hyperthermia. The data suggest that cancer cells can be selectively killed by the combined treatment of menadione and mild hyperthermia, in particular, those tumors existing in the glucose deficient mileau.