REGIONAL HYPERTHERMIA WITH SYSTEMIC CHEMO THERAPY IN CHILDREN AND ADOLESCENTS - FEASIBILITY AND CLINICAL COURSES IN A GROUP OF 34 INTENSIVELY PRETREATED PATIENTS WITH TUMORS OF UNFAVORABLE PROGNOSIS

Temperature elevation for a few degrees (degrees-C) increases signific antly the cytotoxicity of several antineoplastic drugs under experimen tal conditions. An isolated elevation of the tumour temperature, which is possible since a few years, might be able to improve local tumour control without increasing the systemic toxicity. This study was perfo rmed to examine the feasibility of regional hyperthermia with systemic chemotherapy in pediatric patients. The special interests were the le vel of temperatures that could be achieved as well as the degree of to xicity and undesired side effects. Furthermore there was some hope to attain local tumour control in cases with very poor prognosis. 34 pati ents up to 18 years were treated in Munich and Essen until the end of 1992. 21 suffered of local relapse, in 11 cases it was the 2nd up to t he 7th relapse. In another 11 cases the indication for the combined tr eatment was tumour progress or non-response to previous therapy. 33 pa tients were pretreated by aggressive chemotherapy, 20 patients had rec eived radiotherapy before. In 28 cases the tumour was located in the p elvis. The heating device that we use is commercially available. It is based on external electromagnetic radiation which induces heat by abs orption within the tissue. Since the temperature distribution inside t he tumours is very heterogenous thermometry is necessary which can onl y be performed invasively. For this sake we use closed tip catheters w hich are inserted into the tumour by puncture or surgically. The cathe ters remain in place for the whole treatment duration of several weeks . Chemotherapy was performed in treatment cycles (3.4/patient) mainly using etoposide, ifosfamide, and carboplatin. On the 1st and 4th day o f 4 to 5 day courses hyperthermia was performed for 60 minutes simulta neously to drug administration. The tumour temperatures that we achiev ed by this method were within the range where significant enhancement of drug cytotoxicity was shown in preclinical studies. Complications w ere: 2 superficial burns (grade II), 2 systemic complications due to w hole body hyperthermia under general anaesthesia. In 2 of these cases a treatment delay was necessary. We did not observe deep infections of the thermometry catheters. One patient died during a long lasting bon e marrow aplasia. Treatment results are difficult to interprete for th is heterogenous group of patients with prognostically unfavourable con ditions which were intensively treated before and after hyperthermia t reatment. However, in 5 cases the tumours were completely necrotic. 20 % of all patients achieved complete remission for more than a year mai nly by subsequent surgery. 7 patients are in complete remission for up to 64 months. We conclude that the method is feasable since the tempe ratures are satisfactory and complications are tolerable. Therefore ph ase II clinical studies should be performed for regional hyperthermia with systemic chemotherapy in pediatric patients with unfavourable pro gnosis.