Evaluation of systemic tolerance of 42.0 degrees C infrared-A whole-body hyperthermia in combination with hyperglycemia and hyperoxemia. A Phase-I study.

PURPOSE

In September 1965, Manfred von Ardenne presented in the Heidelberg Cancer Research Centre the concept of his so-called systemic Cancer Multistep Therapy--a combined modality treatment including whole-body hyperthermia. At the time, whole-body hyperthermia was attained by a warm water bath plus induced hyperglycemia and a high dosage application of oxygen. After 25 years of basic research, methodical processing and further development of a practical infrared-A hyperthermia technology, the therapy achieved clinical maturity. Within the framework of a clinical phase-I study that was carried out in 1991, we set out to prove the systemic tolerability of systemic Cancer Multistep Therapy.

PATIENTS AND METHODS

103 patients, who had been previously treated with virtually all forms of conventional treatment in its most extensive form and who were in a stage of uncontrollable progression with metastasis growth and/or recurrent primary tumors, were treated within the framework of a clinical phase-I study with the objective of reaching a palliative progression stop. Body core temperatures of 41.8 +/- 0.2 degrees C were attained by means of a special infrared-A machine named IRATHERM 2000 with the aim of reaching a plateau phase of 60 to 70 min. A high dosage of glucose (10% glucose solution, 500 to 700 ml/h, blood glucose level 410 +/- 90 mg/dl) was administered intravenously to intensify lactacidosis and thereby the thermal sensitivity of the malignant tumors to be treated. Using a laminar flow applicator (up to approximately 30 l/min O2 flow), the arterial oxygen partial pressure paO2 was increased to 163 +/- 50 mm Hg. For premedication and neuroleptic analgesia, a combination of dehydrobenzperidol and fentanyl was used. Blood pressure, ECG, oxygen saturation, blood-gas status and hematocrit were monitored continuously and changes in blood electrolyte concentrations were corrected by appropriate intravenous infusions. In terms of systemic tolerability, systemic Cancer Multistep Therapy (whole-body hyperthermia+hyperglycemia+hyperoxemia) induced pathophysiologically no obviously toxic or otherwise detrimental effects. In isolated cases, sporadic erythemas on low perfused skin areas or occasional emesis were observed after the end of the treatment.

RESULTS

The good systemic tolerability of the systemic Cancer Multistep Therapy with only minimal side effects has thus been proven. The hyperthermic IRATHERM machine used to attain the extreme whole-body hyperthermia showed that it was a reliable and practical unit. When UICC criteria and other criteria defined for integrated tumor therapies of systemic character were applied, over 50% of the patients treated had a positive therapeutic response.

CONCLUSION

The good systemic tolerability of the systemic Cancer Multistep Therapy on the one hand, and the positive therapeutic influence on the course of the illness on the other hand, justify the intensified continuation of studies on the effectiveness of systemic Cancer Multistep Therapy.