Clinical Study

A Systemic Hyperthermia Oncologic Working Group Trial
Ifosfamide, Carboplatin, and Etoposide Combined with 41.8°C Whole-Body Hyperthermia for Metastatic Soft Tissue Sarcoma
A.M. Westermann^a, G.J. Wiedemann^b, E. Jager^c, D. Jager^c, D.M. Katschinski^b, A. Knuth^c, P.Z. Vörde sive Vörding^a, J.D.P. Van Dijk^a, J. Finet^d, A. Neumann^c, W. Longo^d, A. Bakhshandeh^b, C.L. Tiggelaar^d, W. Gillis^d, H. Bailey^d, S.O. Peters^b, H.I. Robins<sup>d

a</sup>Academic Medical Center, Amsterdam, The Netherlands;
^bMedical University of Lübeck, Lübeck,
^cKrankenhaus Nordwest, Frankfurt, Germany;
^dUniversity of Wisconsin, Madison, Wisc., USA

Address of Corresponding Author

Oncology 2003;64:312-321 (DOI: 10.1159/000070287)

  Key Words

• Whole-body hyperthermia
• Sarcoma
• Ifosfamide
• Carboplatin

  Abstract

Background: Based on earlier clinical and preclinical studies, we conducted a phase II trial in metastatic sarcoma patients of the combination of 41.8°C (×60 min) radiant heat (Aquatherm^®) whole-body hyperthermia (WBH) with 'ICE' chemotherapy. The ICE regimen consists of ifosfamide (5 g/m²), carboplatin (300 mg/m²) and etoposide (100 mg/m²), concurrent with WBH, with etoposide also on days 2 and 3 post-WBH. Methods: Therapy was delivered every 4 weeks for a maximum of 4 cycles. All patients received filgrastim or lenograstim. Results: Of 108 patients enrolled as of September 2001, 95 are evaluable for response. Of the evaluable patients (mean ECOG performance status ~1; mean age 42.3; 58% male) 33 had no prior therapy for metastatic disease, and 62 were pretreated (mean: 1.5 prior regimens). The overall response rate was 28.4% (4 complete remissions and 23 partial remissions) with stable disease (SD) in 31 patients. For no prior therapy, the response rate was 36%; in pretreated patients it was 24%. The median overall survival by Kaplan-Meier estimates was 393 days (95% CI 327, 496); the median time to treatment failure was 123 days (95% CI 77, 164). The major toxicity (287 cycles) was grade 3 or 4 neutropenia and thrombocytopenia seen in 79.7 and 60.6% of treatments respectively; there were 7 episodes of infection (grade 3/4) with 2 treatment-related deaths, bot involving disease progression and ureteral obstruction. Conclusion: These results are consistent with continued clinical investigation of this combined modality approach.

Copyright © 2003 S. Karger AG, Basel

  Author Contacts

H. Ian Robins, MD, PhD
University of Wisconsin Comprehensive Cancer Center
600 Highland Avenue, Madison, WI 53792 (USA)
Tel. +1 608 263 1416, Fax +1 608 265 8133
E-Mail hirobins@facstaff.wisc.edu

  Article Information

Number of Print Pages : 10
Number of Figures : 3, Number of Tables : 3, Number of References : 50