Phase I study of temozolomide combined with oral etoposide in children with malignant glial tumors

Antonio Ruggiero, Ilaria Lazzareschi, Palma Maurizi, Stefano Mastrangelo, Cesare Colosimo, Daniela Rizzo, Giorgio Attina', Vita Ridola, Riccardo Riccardi, Roberta Migliorati, Patrizia Bertolini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

12 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)513-518
Numero di pagine6
RivistaJournal of Neuro-Oncology
Volume113
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • Administration, Oral
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols
  • Brain Neoplasms
  • Child
  • Child, Preschool
  • Dacarbazine
  • Drug Resistance, Neoplasm
  • Etoposide
  • Female
  • Follow-Up Studies
  • Glioma
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Salvage Therapy

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