Whole Body Hyperthermia: Biological and Clinical Aspects

1. 1 Background neoplastic diseases which are currently refractory to conventional therapy. All aspects of both preclinical Anticancer effects of elevated (noncauterizing) tem­ and clinical WBH, ranging from molecular biology perature were first observed in ancient Egyptian times and physiology to WBH methodologies and clinical (Oleson and Dewhirst 1983). Hippocrates trials, will be comprehensively reviewed. It is our in­ (460-377 B. C. ) later incorporated fever therapy into a tention to provide the reader with a definitive resource homeopathic approach to disease (Le. , treating a dis­ of to evaluate the current status and future potential ease with a symptom of that disease). In the fourth WBH. In so doing, we will attempt to present the vari­ century, Refus of Ephesus advocated the use of fever ous perspectives and insights derived from the efforts induction to treat malignant diseases (Kluger 1980). of investigators throughout the world. We hope this In the nineteenth century tumor regressions accompa­ will encourage an expanded investigative commitment nying high fevers were reported both by Busch and to this exciting and innovative approach to cancer Bruns (Busch 1866; Bruns 1888). At the end of the therapy.

Contenu

1 Introduction.- 1.1 Background.- 1.2 Systemic versus Local and Regional Hyperthermia.- 1.3 Conceptual Approaches to the Therapeutic Use of WBH.- 1.3.1 Drugs.- 1.3.2 Immunotherapy.- 1.3.3 Radiotherapy.- 1.4 Summary.- 2 Hyperthermia and the Immune System.- 2.1 Introduction.- 2.2 In Vitro Studies of Hyperthermia and Immune Effector Cells.- 2.2.1 Macrophages and Hyperthermia.- 2.2.2 Hyperthermia and NK Cells.- 2.2.3 In Vitro Hyperthermia and Biological Response Modifiers.- 2.3 In Vivo Studies: The Abscopal Response and Metastasis.- 2.3.1 NK cells In Vivo.- 2.3.2 Metastasis and Hyperthermia.- 2.4 Clinical Hyperthermia and the Abscopal Response.- 2.5 Clinical WBH and the Immune Response.- 2.6 Conclusions.- 3 WBH and Ionizing Irradiation.- 3.1 Background.- 3.2 Potential Advantages of WBH Compared to Local Hyperthermia.- 3.3 The Importance of Treatment Temperatures Used in Preclinical Studies.- 3.4 Possibly Controllable Clinical Treatment Variables.- 3.5 Clinical Investigations Combining WBH and Ionizing Irradiation.- 3.6 Summary.- 4 WBH and Chemotherapy.- 4.1 Introduction.- 4.2 Potential Mechanisms of Thermal Chemosensitization.- 4.3 Factors Which May Modify Thermal Chemosensitization.- 4.3.1 Heat-drug Sequence.- 4.3.2 Temperature.- 4.3.3 Heating Duration.- 4.3.4 Thermal Tolerance.- 4.3.5 Decreased pH and pO2.- 4.4 Therapeutic Index.- 4.5 Probable Thermal Sensitizing Agents.- 4.6 Future Directions for Preclinical Research.- 4.7 Clinical WBH Studies.- 5 Clinical and Biophysical Aspects of Systemic Hyperthermia.- 5.1 Thermal Regulation and WBH Methodologies.- 5.1.1 Review.- 5.1.2 WBH with a Regional Heat Boost.- 5.1.3 Electromagnetic Technology and WBH.- 5.1.4 Summary.- 5.2 Monitoring Body Site Temperature During WBH.- 5.3 Cardiorespiratory Effects of WBH.- 5.4 Biochemical Effects of WBH.- 5.5 Hematological Changes.- 5.6 Neurological Sequelae.- 5.7 Endocrine Function and WBH.- 5.8 Gastrointestinal Toxicity.- 5.9 Miscellaneous Toxicities.- 6 WBH Animal Studies.- 6.1 Introduction.- 6.2 Large Animals.- 6.3 Murine Models.- 6.4 Special Considerations.- 6.4.1 Species Differences.- 6.4.2 WBH and Metastatic Dissemination.- 7 Special Considerations for the Future.- 7.1 Nononcological Considerations.- 7.1.1 Collagen Vascular Diseases.- 7.1.2 Hypothermia.- 7.1.3 Acquired Immunodeficiency Syndrome.- 7.2 Implications of WBH Research for General Medical Practice.- 7.3 Systemic Hyperthermia: Summary Reflections Regarding Neoplastic Disease.- References.