No abstract

The concept of critical thermal maximum (CTM) has been defined in the literature as the minimal high deep-body temperature that is lethal to an animal. In man the CTM has been estimated at 41.6--42.0 degrees C. Data are presented for sedated, unacclimatized, well-hydrated men heated 1 h at esophageal temperatures of 41.6--42.0 degrees C, without sequelae, except for modest elevation of serum enzymes in two of five patients. These data when combined with other observations in the literature suggest that CTM be redefined as the particular combination of exposure time at elevated body temperatures that results in either subclinical (CTM)s) or clinical (CTMc) injuries. Also presented is a mathematical technique, equivalent time at 42 degrees C (Teq 42 degrees), for expressing hyperthermia in terms of body temperature and exposure time.

The protocol was well tolerated and was associated with antitumor activity in patients with a variety of advanced metastatic solid tumors. Tumor response occurred with the thermochemotherapy treatment despite treating malignancies that had progressed on the same chemotherapy drugs administered as standard treatment. Notably, good responses were observed in patients with high-grade neuroendocrine and pancreas cancers. This regimen will be tested in a phase II study.

The cancer chemotherapeutic cis-dichlorodiammineplatinum (cis-DDP) was administered to 8 patients (1-hr intravenous infusion) at a dose of 70 mg/m2. Plasma and urine concentrations of platinum were determined by flameless atomic absorption spectrometry. Measured plasma platinum concentrations revealed a biphasic clearance of platinum with half-life values of 23 min and 67 hr. Platinum values obtained 3 wk after the infusion indicated that a third excretory phase might be present. Urinary measurements showed 17 +/- 2.7% of the administered dose excreted in the first 4 hr and 23 +/- 3.9% excreted in the first 24 hr. Renal excretion appears to be predominantly by glomerular filtration. Non-protein-bound plasma platinum values were calculated and the non-protein-bound platinum was found to be rapidly and biphasically cleared from the plasma with half-life values of 8 to 10 min and 40 to 45 min.