title: Phase I study of temozolomide combined with oral etoposide in children with malignant glial tumors.
abstract: The treatment of children with malignant glioma remains challenging. The aim of this multicenter phase I study is to establish the recommended dose (RD) of the combination therapy with temozolomide (TMZ) and oral etoposide (VP-16) in children with relapsed or refractory malignant glioma and brainstem glioma at diagnosis. A phase I trial was conducted to establish the maximum tolerated dose (MTD) of TMZ and oral VP-16. This orally administered combination was investigated by a classical 3 + 3 design. Cohorts of patients were enrolled at 4 different levels: (1) TMZ 120 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (2) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-8; (3) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-10; (4) TMZ 150 mg/m(2) on days 1-5 and VP-16 50 mg/m(2) on days 1-12. Therapy was administered in 28-day courses. A total of 118 courses were administered to 18 patients with a median age of 11.2 years. At dose level 1, none displayed toxicity. Of the 6 patients at dose level 2, 1 patient had dose limiting toxicity (DLT). None of the 3 patients at dose level 3 had DLT. At dose level 4, grade III/IV thrombocytopenia and neutropenia were observed in 2 out of the 6 patients enrolled. Therefore, the MTD was established at dose level 3. The RD for phase II trial in children with malignant glial is TMZ 150 mg/m(2) for 5 days and VP-16 50 mg/m(2) for 10 days every 28 days.
authors.affiliation: Pediatric Oncology Division, Department of Pediatric Oncology, A Gemelli Hospital, Catholic University of Rome, Largo A Gemelli 1, 00168 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruggiero
authors.forename: Daniela
authors.initials: D
authors.lastname: Rizzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Attinà
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lazzareschi
authors.forename: Palma
authors.initials: P
authors.lastname: Maurizi
authors.forename: Vita
authors.initials: V
authors.lastname: Ridola
authors.forename: Stefano
authors.initials: S
authors.lastname: Mastrangelo
authors.forename: Roberta
authors.initials: R
authors.lastname: Migliorati
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bertolini
authors.forename: Cesare
authors.initials: C
authors.lastname: Colosimo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D016879:Salvage Therapy; D000077204:Temozolomide
chemical_list: D005047:Etoposide; D003606:Dacarbazine; D000077204:Temozolomide