Intracorporeal whole body hyperthermia: toxicity assessment.
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Animals↗
Biomedical subjects
M Mentzel
Publications and source records attributed to M Mentzel.
Dynamic changes in serum erythropoietin levels in solid tumour patients undergoing 41.8 degrees C whole body hyperthermia and/or chemotherapy.
Whole Body Hyperthermia (WBH) has been shown to have physiological effects on myeloid and megakaryocytic haematopoietic tissue via both cytokine induction, as well as hormonal changes. In order to extend this knowledge base to the erythroid cells, endogenous erythropoietin (EPO) levels were studied in 17 cancer patients receiving 41.8 degrees C WBH and/or chemotherapy, as well as in 53 anaemic and non-anaemic control patients. Pre-treatment EPO levels showed a 'blunted' EPO response in cancer patients compared to the control patients. Post-treatment data demonstrated a significant chemotherapy induced increase in EPO levels with a peak at 36 to 48 hours (independent of changes in haemoglobin) and 10 to 13 days post chemotherapy (simultaneously with a drop in haemoglobin levels). The early change in EPO levels was not influenced by the addition of 41.8 degrees C (x 60 min) WBH to the same chemotherapy regimen, i.e., ifosfamide, carboplatin, and etoposide. Taken collectively, our data show that endogenous EPO levels in cancer patients can be effected by chemotherapy (independent of changes in haemoglobin). This EPO response to chemotherapy is not impacted on by 41.8 degrees C WBH. A relevant secondary conclusion can also be derived from this investigation, i.e., caution should be exercised as to the use of EPO levels during chemotherapy as predictors of exogenous EPO efficacy.
Adult↗
Influence of circadian rhythm on 41.8 degrees C whole body hyperthermia induction of haematopoietic growth factors.
It has previously been reported by the authors that the induction of a series of cytokines by 41.8 degrees C Whole Body Hyperthermia (WBH), i.e., interleukin (IL)-1 beta, IL-6, IL-8, IL-10, tumour necrosis factor alpha, and granulocyte colony stimulating factor (G-CSF). As cytokine levels are known to fluctuate as a function of time, i.e. circadian rhythm, the influence of circadian time structure on specific haemotopoetic growth factors is studied, i.e. granulocyte macrophage colony stimulating factor (GM-CSF), G-CSF and IL-3. Samples derived from four cancer patients undergoing extracorporeal WBH resulted in the following observations: G-CSF is induced by WBH, but unaffected by circadian rhythm, IL-3 fluctuates with circadian rhythm, but is unaffected by WBH. Specifically, a biphasic temporal pattern of IL-3 (i.e. with a peak at 2:00 and 5:00 a.m. and a nadir concentration at 5:00 p.m.) was found by analysis of variance. GM-CSF was below the lower detection limit pre and post WBH. The data show the importance of measuring cytokines as a function of time to circumvent conflicting results in the inter-relationship of 'true' cytokine induction and circadian rhythm. The implications of the differential induction of G-CSF, GM-CSF, and IL-3 for myeloprotection after WBH are discussed.
Circadian Rhythm↗
Systemic hyperthermia and ICE chemotherapy for sarcoma patients: rationale and clinical status.
Preclinical studies are consistent with the concept that 41.8 degrees C whole body hyperthermia (WBH) can enhance the therapeutic index of specific chemotherapeutic agents. These laboratory investigations resulted in 2 phase I clinical studies, which also support this hypothesis. These trials were extended to 2 sequential phase II investigations of WBH plus ifosfamide, carboplatin and etoposide (ICE) for refractory sarcoma patients. The first study (involving 12 patients) using extra-corporeal WBH was prematurely closed to adopt a less toxic WBH technology, i.e., the radiant heat Aquatherm. To date, 12 patients have been accrued to the Aquatherm trial. Projections regarding reduced morbidity were correct. The response rate for ICE/WBH is currently 63%. The review to follow will summarize the results of these trials, as well as the laboratory and clinical data which serve to explicate the dramatic clinical results observed to date.
Antineoplastic Combined Chemotherapy Protocols↗