title: Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.
abstract: From July 1986 to 1990, 65 patients with deep-seated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40 patients) had received ifosfamide-containing drug regimens before entering the RHT study, 26% (17 patients) were pretreated by surgery and/or radiation and 12% (8 patients) were treated primarily. A total of 426 RHT treatments (mean 6.6 RHT/patient) were applied predominantly within the pelvic region (82%) bearing relative large tumours (mean volume 500 cm3). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1-5), etoposide (100 mg/m2, days 1, 3, 5) and 2-mercaptoethanesulphonic acid (mesna; 300 mg/m2 x 4, days 1-5) with RHT only given on days 1 and 5 in repeated cycles every 4 weeks. Detailed thermal mapping by invasive thermometry was performed in all patients. In 61 patients evaluable for tumour control the overall objective response rate including 9 complete responders (CR), 4 partial responders (PR) and 8 patients with favourable histological response (FHR) was 34% (95% confidence limits, 23%-46%). Following CR, the patients are alive and remain disease-free (mean disease-free survival 15.6 months). Of the patients with PR and FHR, 3 died from metastatic and/or local disease after 4, 17, and 39 months, and 1 patient died from other disease (acute myelocytic leukemia) after 27 months. The other 8 patients remain stable at 29, 25, 17, 11, 10, 8, 7, and 6 months. Twenty-two patients revealed no change and 18 patients showed local tumour progression (PD). Side-effects of RHT were tolerable and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. By analysis of temperature parameters, the time-averaged temperatures of all RHT treatments calculated for 20% (T20), 50% (T50) or 90% (T90) of measured tumour sites differed significantly between responders (CR + PR + FHR) and non-responders (PD), respectively (T20, P = 0.001; T50, P = 0.0005; T90, P = 0.0001). the data further support a strong potential for ifosfamide plus etoposide combined with RHT in pretreated patients with advanced sarcomas.
authors.affiliation: Institut für Klinische Hämatologie, University of Munich, Federal Republic of Germany.
authors.forename: R D
authors.initials: RD
authors.lastname: Issels
authors.forename: J
authors.initials: J
authors.lastname: Mittermüller
authors.forename: A
authors.initials: A
authors.lastname: Gerl
authors.forename: W
authors.initials: W
authors.lastname: Simon
authors.forename: A
authors.initials: A
authors.lastname: Ortmaier
authors.forename: C
authors.initials: C
authors.lastname: Denzlinger
authors.forename: H
authors.initials: H
authors.lastname: Sauer
authors.forename: W
authors.initials: W
authors.lastname: Wilmanns
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012509:Sarcoma / Q000628:therapy*
chemical_list: D005047:Etoposide; D007069:Ifosfamide