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

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.

• Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, James E Herndon 2nd, April Coan, Sridharan Gururangan, Katherine B Peters, Roger McLendon, Sith Sathornsumetee, Jeremy N Rich, Eric S Lipp, Dorothea Janney, Henry S Friedman
• Journal: Cancer (Cancer) Vol. 118 Issue 19 Pg. 4759-67 (Oct 01 2012) ISSN: 1097-0142 [Electronic] United States
• PMID: 22371319 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2012 American Cancer Society.

Chemical References

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

Topics

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