Etoposide toxicity on human neuroblastoma cells in vitro is enhanced by preceeding hyperthermia.

BACKGROUND: Thermal enhancement has been proven in vitro for the cytotoxic effect of alkylants and platinum compounds, not, however, for etoposide, which acts synergistically to these drugs. PROCEDURE: Our in vitro study on a neuroblastoma cell line confirmed previous results in other tumor models that the cytotoxicity of etoposide (12.8% as compared to untreated controls) is not enhanced by simultaneous heating to 40 or 42 degrees C for 1 hr (11.9%), as jugded by colony forming assay. RESULTS: The same temperature applied 24 hr before the drug resulted in a significant decrease of colonies (6.1%). Double treatment with etoposide within a 24-hr-interval yielded a similar result (5.6%). The colony number could be further decreased by adding hyperthermia 24 hr before the second treatment (1.3%). CONCLUSIONS: We demonstrate in vitro that the enhancing effect of increased temperature on the cytotoxicity of etoposide on neuroblastoma cells is not absent, but depends on scheduling. The temperature range used is achievable in total body hyperthermia. Thus, our results are relevant for possible treatment of disseminated neuroblastoma.

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

Patients with recurrent, progressed or otherwise, therapy resistant malignancies, whose diseases are not amenable to standard therapies, may benefit from hyperthermia (HT). Based on the number of 1600 newly diagnosed malignancies, in patients < 15 years of age, per annum of which 70% are successfully treated on the standard treatment protocols of the German Society of Pediatric Oncology and Hematology (GPOH) and allowing for various drop-outs for reasons such as lack of established protocols, insufficient state of health and others, this means that as many as 100 children per annum can be expected to be enrolled into phase I/II trials in Germany. In view of the promising results in adults, phase I/II HT studies have also been performed in children and adolescents with recurrent or advanced malignancies including Ewing's tumours, aggressive fibromatosis, and germ cell tumours. Recent results in paediatric studies indicate the feasibility of both regional deep HT and whole body HT, and the best case analysis reveals promising response rates (CR + PR) as well as some long-term remissions. Technical modifications, due to the smaller body diameters, led to mean intratumoural temperatures in paediatric patients similar to those reported for adults in whom an improved outcome was demonstrated. The results in children and adolescents even suggest that introduction of HT into standard treatment protocols may be promising to improve tumour response and event-free survival in patients with poor risk malignancies of childhood.

ESHO quality assurance guidelines for regional hyperthermia.

The Technical Committee and the Clinical Committee of the ESHO evaluated the experience of the institutes which are active in clinical regional hyperthermia using radiative equipment. Based on this evaluation, QA guidelines have been formulated. The focus of these guidelines lies on what must be done not on how it should be done. Subjects covered are: treatment planning, treatment, treatment documentation, requirements and characterization of equipment, safety aspects, hyperthermia staff requirements and instrumentation for quality assurance.

Treatment of children with relapsed soft tissue sarcoma: report of the German CESS/CWS REZ 91 trial.

BACKGROUND: The present study was performed to evaluate the possibilities of relapse treatment in patients heavily pretreated for a soft tissue sarcoma. PATIENTS AND METHODS: Prospective, multicenter study in 44 soft tissue sarcoma (STS) patients with first relapse. Primary diagnosis was embryonal rhabdomyosarcoma (RME) in 17 patients, alveolar rhabdomyosarcoma (RMA) in 13, primitive neuroectodermal tumor (PNET) in 6, and miscellaneous soft tissue sarcomas in 8 patients. Initial chemotherapy consisted of carboplatin/etoposide combination (150 mg/m2 each, days 1 to 4) followed by local therapy including surgical treatment and, whenever possible, radiotherapy. RESULTS: In 11/17 patients without primary tumor resection, CR or PR was achieved following the initial two cycles of chemotherapy (61%). The probability of event-free survival (pEFS) for RME patients was 0.41 +/- 0.12 at 5 years, and 0.25 +/- 0.12 for RMA patients. But, in contrast no PNET patient or patient with another soft-tissue sarcoma achieved long-term remission. Additional local radiotherapy significantly (P = 0.002) improved pEFS (3-year estimates of 0.23 +/- 0.2 vs. 0.1 +/- 0.1 in patients without radiotherapy). CONCLUSIONS: In patients with RME, relapse treatment employing a carboplatin/etoposide combination may induce a second remission in approximately 40% of patients. Surgical excision and additional local radiotherapy seem to be essential to maintain a stable remission. In patients with RMA or PNET, however, this treatment strategy is of no long-term benefit.