A Systemic Hyperthermia Oncologic Working Group Trial

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/m 2 ), carboplatin (300 mg/m 2 ) and etoposide (100 mg/m 2 ), 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.