Clinical application of hyperthermia combined with anticancer drugs for the treatment of solid tumors

Background. Hyperthermia is one of the modalities used to treat various forms of malignancies, including esophageal, stomach, or rectal cancers. Methods. The basic mechanism of synergism between hyperthermia and anticancer drugs, as well as the clinical result of hyperthermia for the treatment of gastrointestinal malignancy, was reviewed. Results. Hyperthermia exerts a cytotoxic effect in combination with various mechanisms. Hyperthermia is applied in combination with chemotherapy and/or radiotherapy in the clinical setting. Among the anticancer drugs that are synergistic with hyperthermia is cisplatin, which is prevalent for clinical application. The mechanism of enhanced cytotoxicity of cisplatin includes increased intracellular drug accumulation, increased platinum-DNA adducts, and inhibition of DNA repair. At our institute, hyperthermochemoradiotherapy was conducted as a neoadjuvant therapy for either operative cases or as a palliative therapy for unresectable cases for esophageal and rectal cancers. In both situations, hyperthermochemoradiotherapy showed an excellent benefit in both the control of local recurrence and and in an improvement in patient survival. Regarding gastric cancer, the most popular application of hyperthermia was the intraoperative hyperthermic peritoneal lavage with cisplatin. This treatment modality demonstrated a better control of the disseminated lesion. Regarding the factors that influence thermosensitivity, in vitro experiments demonstrated the heat-shock proteins or tumor suppressor gene p53 to be related to thermosensitivity. In the clinical setting, these factors remain to be firmly established as predictive factors for thermosensitivity. Conclusions. It is evident that hyperthermia was effective in the control of far-advanced gastrointestinal malignancies. When more reliable factors for the prediction of the treatment response can be established, the standard guidelines for the application of hyperthermia can then be made.