Phase II study of Gleevec plus hydroxyurea in adults with progressive or recurrent low-grade glioma

Cancer. 2012 Oct 1;118(19):4759-67. doi: 10.1002/cncr.26541. Epub 2012 Feb 27.

Abstract

Background: We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma.

Methods: A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on enzyme-inducing antiepileptic drugs (EIAEDs) and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free survival at 12 months (PFS-12) and secondary endpoints were safety, median progression-free survival, and radiographic response rate.

Results: Thirty-two patients were enrolled into each cohort. Eleven patients (17%) had before radiotherapy and 24 (38%) had received before chemotherapy. The median PFS and PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%), and diarrhea (3%).

Conclusions: Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible antitumor activity.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Astrocytoma / drug therapy*
  • Astrocytoma / mortality
  • Benzamides
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Cohort Studies
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Diarrhea / chemically induced
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / adverse effects
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neutropenia / chemically induced
  • Oligodendroglioma / drug therapy*
  • Oligodendroglioma / mortality
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Temozolomide
  • Thrombocytopenia / chemically induced
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Dacarbazine
  • Imatinib Mesylate
  • Hydroxyurea
  • Temozolomide