This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiedemann, G. J. Articles by Wagner, T. Search for Related Content PubMed PubMed Citation Articles by Wiedemann, G. J. Articles by Wagner, T.

Ifosfamide and Carboplatin Combined with 41.8°C Whole-Body Hyperthermia in Patients with Refractory Sarcoma and Malignant Teratoma¹

Departments of Internal Medicine [G. J. W., E. K., M. M., J. G., T. W.], Anesthesiology [S. E., P. S.], Immunology [M. K.], Radiotherapy [T. F.], and Physiology [S. F., C. W.], University of Lübeck, Ratzeburger Allee 160, D-23538, and University Children's Hospital, Lübeck [P. B.], and University Children's Hospital, Tübingen [F. d'O.), Germany

The purpose of this study was to evaluate the pharmacokinetics, biological interactions, and toxicities of ifosfamide and carboplatin combined with 41.8°C whole-body hyperthermia (WBH) for 1 h in a pilot clinical study. Nineteen patients with refractory sarcoma or malignant teratoma were treated. To obtain baseline pharmacokinetic data for ifosfamide, the first chemotherapy course was given without WBH in six patients. This enabled comparison of systemic toxicity and pharmacokinetics of the drug combination with and without WBH (± WBH). All other patients received three thermochemotherapy treatments every 3 weeks. Ifosfamide was escalated from 5 to 10 g/m² with a fixed carboplatin dose of 480 mg/m². WBH was induced by extracorporally heated blood (in a hemodialysis apparatus) with general anesthesia. The drugs were given at target temperature. A total of 49 thermochemotherapy treatments was administered. The use of the hemodialysis device resulted in an approximate one-third reduction of blood concentrations of 4-hydroxyifosfamide, one activated intermediate metabolite of ifosfamide and carboplatin, but in an increase of chloroacetaldehyde, the other main ifosfamide metabolite. The WBC counts and the platelet nadirs (up to WBH grade 4) were not significantly different ± WBH. Of 19 evaluable patients, 7 partial remissions, 8 disease stabilizations (average duration, 3 months), and 4 patients with progressive disease were observed. There was no WBH-related mortality. Toxicities observed included mild (anasarca, diarrhea, pressure sores, and perioral herpes simplex) and severe (reversible neuropathy, cardiopulmonary distress, and severe renal dysfunction). No hepatic or central nervous system toxicity occurred. Nephropathy was the dose-limiting toxicity. In conclusion, ifosfamide and carboplatin can be administered with extracorporally induced WBH with acceptable toxicity. Results obtained are consistent with continued evaluation of this combined modality approach.

¹ This work was supported by Deutsche Forschungsgemeinschaft DFG (Grant Wi 1152/1-1) and Werner und Klara Kreitz-Stiftung, Kiel, Germany.

² To whom requests for reprints should be addressed.

Received 4/ 1/94. Accepted 8/18/94.

This article has been cited by other articles:

				S. Hegewisch-Becker, K. Braun, M. Otte, A. Corovic, D. Atanackovic, A. Nierhaus, D. K. Hossfeld, and K. Pantel Effects of Whole Body Hyperthermia (41.8{degrees}C) on the Frequency of Tumor Cells in the Peripheral Blood of Patients with Advanced Malignancies Clin. Cancer Res., June 1, 2003; 9(6): 2079 - 2084. [Abstract] [Full Text] [PDF]

				A. Bakhshandeh, V. Bath, G. J Wiedemann, W. Longo, B. M Lerner, C. L Tiggelaar, and H I. Robins Year 2000 guidelines for clinical practice of whole body hyperthermia combined with cytotoxic drugs from the University of Lubeck and the University of Wisconsin Journal of Oncology Pharmacy Practice, September 1, 1999; 5(3): 131 - 134. [PDF]

				H. Pagel Evaluating the nephrotoxicity of cytotoxic agents using a rat kidney perfusing model Journal of Oncology Pharmacy Practice, December 1, 1998; 4(4): 218 - 226. [Abstract] [PDF]