Posters— Medical Oncology

WHOLE BODY HYPERTHERMIA (41.8°C) COMBINED WITH IFOSFAMIDE (IFO), CARBOPLATIN (CBDCA) AND ETOPOSIDE (VP-16) IN PATIENTS WITH UNTREATED AND RELAPSED/REFRACTORY SOFT TISSUE SARCOMA

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 41.8°C (x60 min) radiant heat WBH with ICE chemotherapy ( IFO 5g/m2, d1; CBDCA 300 mg/m2,d1; VP-16 100 mg/m2, d1-3). 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. All pts. required G-CSF. Therapy was delivered every 4 weeks for a maximum of 4 cycles. During WBH treatments pts. received total intravenous anesthesia with target controlled propofol infusion.

12 untreated and 11 relapsed/refractory pts. have been entered onto the study thus far. All relapsed/refractory pts. were pretreated with adriamycin and IFO containing regimens. Pathology: malignant fibrous histiocytoma 7, leiomyosarcoma 6, GIST 5, other types 5. So far 58 treatment cycles have been administered. WHO grade 3 and 4 neutropenia and thrombopenia were substantial and occurred in 41% and 31% of episodes, respectively leading to a dose reduction in 19% of episodes. Neutropenic fever was seen in 22% of episodes. Other toxicities including renal, hepatic, neurological, mucositis and nausea were mild. Concerning the degree of toxicity there was no significant difference between chemotherapy naive and pretreated pts. Responses: 10/12 untreated pts. are so far evaluable with 3 PR, 4 SD and 2 PD, representing a clinical benefit of 70%. The PR’s included 1 leiomyosarcoma and 1 GIST. 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.

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.