Systemic Hyperthermia Combined with Chemotherapy: A Pilot Clinical Trial in the Treatment of Metastatic Gastrointestinal Cancers

Background: Hyperthermia, which involves heating body tissues to enhance cancer treatment efficacy, has been explored as an adjunctive therapy to improve chemotherapy outcomes. Whole-body hyperthermia (WBH) offers a potential synergistic approach by sensitizing cancer cells to chemotherapeutic agents and enhancing drug delivery. Objectives: This study aimed to evaluate the efficacy and safety of combining systemic chemotherapy with WBH in patients with metastatic gastrointestinal cancers. Methods: A pilot study was conducted at Shohada Tajrish Hospital. Patients with pathologically confirmed metastatic gastrointestinal cancers were treated with standard systemic chemotherapy combined with WBH. Hyperthermia was applied using infrared devices, maintaining body temperatures between 39°C and 40.5°C. Patients were kept at this plateau for 1.5 hours, receiving chemotherapy concurrently. Chemotherapy drugs were administered at 80% of the standard dose. After the completion of WBH, patients were observed in the hospital for 24 hours to ensure safety. Data on patient demographics, tumor characteristics, chemotherapy regimens, and adverse events were systematically collected and analyzed. Results: A total of 20 patients (mean age: 54.8 years) participated in the study, with an equal distribution of male and female participants. The mean number of hyperthermia and chemotherapy cycles was 4.6 and 4.9, respectively. Clinical response rates included 5% (1 patient) with a complete response (CR), 40% (8 patients) with a partial response (PR), and 35% (7 patients) with stable disease (SD). The overall disease control rate (DCR) — comprising CR, PR, and SD — was 80%, and all responses were observed in patients who had received at least six cycles of hyperthermia. Most patients experienced either no adverse events or only grade 1 toxicities. The most frequently observed grade 1 adverse effects were diarrhea (45%) and vomiting (43%), indicating that gastrointestinal symptoms were common. Severe toxicities (grade 4) were rare, occurring in approximately 2% of cases. Conclusions: Whole-body hyperthermia combined with chemotherapy is a viable and well-tolerated therapeutic strategy for metastatic gastrointestinal cancers, demonstrating a favorable toxicity profile and promising response rates. Additional large-scale studies are suggested to confirm these findings and investigate the mechanisms underlying the improved treatment efficacy.