A phase I study of irinotecan in combination with metronomic temozolomide in patients with recurrent glioblastoma

Autores de IIS La Fe

• Gaspar Reynes Muntaner

  Autor

Participantes ajenos a IIS La Fe

• Balana, C
• Gallego, O
• Iglesias, L
• Perez, P
• Garcia, JL

Grupos

• Investigación Clínica y Traslacional en Cáncer

  

  Leader

  José Gómez Codina

Abstract

To determine the maximum tolerated dose of irinotecan administered every 2 weeks, in combination with a fixed and continuous administration of temozolomide, in patients with glioblastoma at first relapse. Patients received oral temozolomide at a fixed and continuous dose of 50mg/m(2) divided into three daily doses, except for a single 100mg/m(2) dose, administered before every irinotecan infusion. Irinotecan was given intravenously on days 8 and 22 of 28-day cycles. The starting dose of irinotecan was 100mg/m(2), and this was escalated by increments of 15mg/m(2) in cohorts of 3-6 evaluable patients. Determination of the dose-limiting toxicity was based on toxicities recorded from day 1 of the first cycle to day 8 of the third cycle. Enzyme-inducing antiepileptic drugs were not allowed. Tumor response was assessed by MRI every 8 weeks. Twelve patients were enrolled in this phase I study. The three patients enrolled at dose level 1 and six of nine patients enrolled at dose level 2 were evaluable for toxicity. The maximum tolerated dose of irinotecan was 100mg/m(2). The dose-limiting toxicities were hematologic and gastrointestinal. Nine patients were evaluable for response: one patient achieved a partial response, four patients remained stable, and four patients had disease progression. The combination of metronomic temozolomide and irinotecan every 2 weeks can be safely administered at the recommended doses; a phase II study with this combination was started and has completed accrual. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Keywords

• irinotecan; metronomic chemotherapy; phase I; recurrent glioblastoma; temozolomide