title: Transcranial electro-hyperthermia combined with alkylating chemotherapy in patients with relapsed high-grade gliomas: phase I clinical results.
abstract: Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating chemotherapy is occasionally used as salvage treatment in the relapse of patients with high-grade gliomas. Experimental data and retrospective studies suggest potential effects. However, no prospective clinical results are available. We performed a single-center prospective non-controlled single-arm Phase I trial. Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age 18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose-escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade gliomas were included. Relevant toxicities were local pain and increased focal neurological signs or intracranial pressure. No DLT occurred. In some patients, the administration of mannitol during EHT or long-term use of corticosteroids was necessary to resolve symptoms. Although some patients showed responses in their primarily treated sites, the pattern of response was not well defined. EHT plus alkylating chemotherapy is tolerable in patients with relapse of high-grade gliomas. Episodes of intracranial pressure were, at least, possibly attributed to EHT but did not cause DLTs. A Phase II trial targeting treatment effects is warranted on the basis of the results raised in this trial.
authors.affiliation: Department of Neurology, University of Regensburg Medical School (UKR), Universitätsstrasse 84, 93053, Regensburg, Germany.
authors.forename: Caecilia
authors.initials: C
authors.lastname: Wismeth
authors.forename: Christine
authors.initials: C
authors.lastname: Dudel
authors.forename: Christina
authors.initials: C
authors.lastname: Pascher
authors.forename: Paul
authors.initials: P
authors.lastname: Ramm
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Birgit
authors.initials: B
authors.lastname: Hirschmann
authors.forename: Christiane
authors.initials: C
authors.lastname: Reinert
authors.forename: Martin
authors.initials: M
authors.lastname: Proescholdt
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuierer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods*; D005260:Female; D005910:Glioma / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating