Regionale Hyperthermie mit systemischer Chemotherapie bei Kindern und Jugendlichen: Durchführbarkeit und klinische Verläufe bei 34 intensiv vorbehandelten Patienten mit prognostisch ungünstigen Tumorerkrankungen

Abstract

Temperature elevation for a few degrees (degrees C) increases significantly the cytotoxicity of several antineoplastic drugs under experimental 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 performed to examine the feasibility of regional hyperthermia with systemic chemotherapy in pediatric patients. The special interests were the level of temperatures that could be achieved as well as the degree of toxicity and undesired side effects. Furthermore there was some hope to attain local tumour control in cases with very poor prognosis. 34 patients 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 the 7th relapse. In another 11 cases the indication for the combined treatment was tumour progress or non-response to previous therapy. 33 patients were pretreated by aggressive chemotherapy, 20 patients had received radiotherapy before. In 28 cases the tumour was located in the pelvis. The heating device that we use is commercially available. It is based on external electromagnetic radiation which induces heat by absorption within the tissue. Since the temperature distribution inside the tumours is very heterogeneous thermometry is necessary which can only be performed invasively. For this sake we use closed tip catheters which are inserted into the tumour by puncture or surgically. The catheters 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperthermia in oncology

“…The consecutive phase II protocol (RHT-91) was designed as a neoadjuvant study where the EIA regimen (etoposide, ifosfamide, adriamycin) was given to 59 patients with highrisk soft tissue sarcomas (size 8 cm, grade II/III, extracompartimental) for four cycles prior to surgical resection. After a ® rst initial analysis, showing no severe toxicity or unexpected treatment side eOE ects (Issels et al 1993), the evaluation of clinical and pathohistological response was 47% . At present, 29 patients are alive and the median follow-up of all patients is now more than 3.5 years.…”

Estimated number of children with cancer eligible for hyperthermia based on population- and treatment-related criteria

“…Int J Hyperthermia Downloaded from informahealthcare.com by University of Toronto on 12/03/14 patient diameters and the di erent heat applicators (Sigma-30, Sigma-40, BSD medical corporation, Salt Lake City, USA), in children and adolescents, intratumoural temperatures could be achieved which were in a similar range of magnitude to those for which bene® cial e ects could be demonstrated in adults (Willnow et al 1989, Romanowski et al 1993, Wessalowski et al 1998. Additionally, various working groups were already able to show a bene® cial e ect of chemotherapy and HT in terms of partial and complete remissions, and even cures in refractory paediatric tumours, thus illustrating the general value of HT treatment in paediatric cancer (table 7).…”

“…Other study groups have focused on treatment strategies with additional HT in childhood cancer. Although some pre-clinical (Cavaliere et al 1967, Hofer et al 1976, Willnow 1981, Moriyama et al 1986, 1993, Rama and Prasad 1986, Koole and Schipper 1990, Page et al 1992, Wiedemann et al 1992 and clinical studies in paediatric oncology (Schipper et al 1987, Otte 1988, Willnow et al 1989, Romanowski et al 1993, Wessalowski et al 1998) disclosed an objective heat-induced response modi® cation of chemotherapy radiotherapy, especially in tumours that failed to respond to standard therapies, various ethical and clinical aspects have to be considered for an appropriate case selection in childhood cancer. The goals which must be addressed in the selection of a patient population which can bene® t from HT must be (a) an improved rate of remissions, (b) a decrease in mutilating surgical procedures, and (c) the avoidance of high-dose radiation, particularily in infants and toddlers.…”

Regional hyperthermia combined with chemotherapy in paediatric, adolescent and young adult patients: current and future perspectives

“…The data on RHT or hyperthermic chemotherapy in children and adolescents are currently limited, and only two active German hyperthermia centres treating paediatric patients were identified, the Heinrich Heine University Hospital Düsseldorf and the Charité-Universitätsmedizin Berlin. The study by Romanowski et al was the first which combined RHT and systemic chemotherapy (ICE: etoposide 4 × 150 mg/m 2 and ifosfamide 4 × 2000 mg/m 2 or carboplatin 4 x 150 mg/m 2 ) in 34 intensively pretreated children and adolescents with prognostically unfavourable tumour diseases [ 10 ]. Romanowski et al reported that 20 % of patients experienced a complete remission and 7 patients remained alive up to 64 months after the combined treatment.…”