An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.
BACKGROUND
Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control.


METHODS
From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas.


METHODS
locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4.


RESULTS
In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively.


CONCLUSIONS
TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.
Wessalowski
R
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Clinik of Pediatric Oncology, Hematology and Immunology, Heinrich Heine Universität Düsseldorf, Germany. wessalowski@med.uni-duesseldorf.de
Schneider
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DT
Mils
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Hannen
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Calaminus
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Engelbrecht
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Pape
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Willers
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Engert
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Harms
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Göbel
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D000008:Abdominal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D002813:Chondrosarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003627:Data Interpretation, Statistical; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018237:Germinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000627:therapeutic use*; D007223:Infant; D017567:Karnofsky Performance Status; D008159:Lumbar Vertebrae; D008297:Male; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D010386:Pelvic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012509:Sarcoma / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D013125:Spinal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide