
Whole-body hyperthermia combined with chemotherapy can be shown to increase tumor cell death without increasing bone marrow suppression.  [23]

In one study, seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with BCNU [a chemotherapy agent]. All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases. [113]

In another study, 10 of 12 adult patients with refractory sarcoma had a response or stable disease after entering a phase II trial of 41.8 degrees C (x 60 min) extracorporeal whole body hyperthermia (WBH) with ICE, [ifosfamide, carboplatin, etoposide. 8 patients had a history of prior chemotherapy associated with disease progression. Following WBH/ICE, 7 partial remissions were observed (58%); 3 patients experienced disease stabilisation; the aforementioned 10 patients each received four cycles of therapy. 2 patients exhibited progressive disease. Major toxicities were targeted to bone marrow and kidneys.  Minor toxicities included anasarca, diarrhea, irregular heartbeats, pressure sores, and oral herpes simplex sores. [76]

In a third study, 11 patients with advanced soft tissue sarcoma were treated with whole body hyperthermia (41.8 degrees C-43.0 degrees C) for 2 hours, doxorubicin (45 mg/m2) at the beginning of peak temperature and cyclophosphamide (1000 mg/m2) 6 hours after doxorubicin. Warming was accomplished with a nylon and vinyl mesh water perfused suit and heating blankets under barbiturate anesthesia. Thirty-five thermochemotherapy treatments were administered after an initial baseline euthermic course. There were two complete and two partial responses including three of three liposarcomas and one of two leiomyosarcomas, and there were two disease stabilizations. Morbidity included anasarca, nausea and vomiting, diarrhea, myalgias, mild surface burns, perioral herpes simplex, reversible neuropathy, hypotension, and cardiac arrhythmias. Hyperglycemia and hypophosphatemia were found during heating, and normalized at 24 hours. Liver enzyme elevations occurred 24 hours after heating and normalized within 1 week. A uniform platelet decrease (mean, 107,000/microliter) was found at 24 hours. Thermochemotherapy was found to be a feasible approach for selected patients with advanced soft tissue sarcoma for the subset of liposarcomas and leiomyosarcomas. [157]

"Hyperthermia is known to enhance the therapeutic index of numerous cytotoxic drugs, including alkylating agents and platinum derivatives. Due to technical improvement WBH has become a feasible treatment option as an adjunct to standard chemotherapy. Earlier clinical trials have produced promising results in relapsed/refractory sarcoma (Wiedemann et al., 1996) by combining ... WBH with ICE chemotherapy. ... We therefore started a phase II clinical trial to investigate efficacy and feasibility in untreated and relapsed/refractory soft tissue sarcoma using an identical protocol. ..."[3*]

12 untreated and 11 relapsed/refractory patients were entered into the study: 6 were LMS and 5 were GIST.... 
Previously untreated responses:  10 previously untreated patients were evaluable, with 3 PR [one a leiomyosarcoma and one a GIST], 4 SD and 2 PD.  Apparent response rate is 70%.  [3*]

"All pts in the relapsed/refractory group are evaluable with 2 minor responses, 4 SD and 4 PD, representing a clinical benefit of 56%. We had 1 early death in each group, one due to tumor lysis and one due to sepsis. The median time to progression and median survival by Kaplan-Meier estimates is not reached in de novo pts. and is 18 weeks (range 0-81) and 66 weeks (range 1-112), respectively for relapsed/refractory pts." [3*]

"Conclusion: concerning PR rates in relapsed/refractory sarcoma, we could not reproduce the promising results, reported elsewhere (PR rate of 25%, Wiedemann et al., ASCO 2000) in our small series of pts. This may be due to a more intense pretreatment. Nevertheless, results concerning clinical benefit especially in untreated pts. are encouraging and warrant further investigation. Updated results will be presented at the meeting. "[3*]
