Randomized phase II trial of chemoradiotherapy followed by either dose-dense or metronomic temozolomide for newly diagnosed glio

Primary tabs

field_vote: 
Average: 8 (1 vote)
Publication type: 
Number of included patients: 
References: 
Disease(s): 
Therapeutic Substance(s): 

Randomized phase II trial of chemoradiotherapy followed by either
dose-dense or metronomic temozolomide for newly diagnosed glioblastoma.

 
Clarke JL, Iwamoto FM, Sul J, Panageas K, Lassman AB, DeAngelis LM, Hormigo A, Nolan CP, Gavrilovic I, Karimi S, Abrey LE.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY10065, USA.
 
PURPOSE:
Alternative dosing schedules of temozolomide may improve survival in
patients with newly diagnosed glioblastoma (GBM) by increasing the
therapeutic index, overcoming common mechanisms of temozolomide
resistance, or both. The goal of this randomized phase II study was to
evaluate two different temozolomide regimens in the adjuvant treatment
of newly diagnosed GBM.
PATIENTS AND METHODS: Adult patients with newly
diagnosed GBM were randomly assigned to receive standard radiotherapy
with concurrent daily temozolomide followed by six adjuvant cycles of
either dose-dense (150 mg/m(2) days 1 to 7 and 15 to 21) or metronomic
(50 mg/m(2) continuous daily) temozolomide. Maintenance doses of
13-cis-retinoic acid were then administered until tumor progression.
The primary end point was overall survival (OS) at 1 year. Tumor tissue
was assayed to determine O(6)-methylguanine-DNA methyltransferase
(MGMT) promoter methylation status.
RESULTS: Eighty-five eligible
patients were enrolled; 42 were randomly assigned to dose-dense and 43
to metronomic temozolomide. The 1-year survival rate was 80% for the
dose-dense arm and 69% for the metronomic arm; median OS was 17.1
months (95% CI, 14.0 to 28.1 months) and 15.1 months (95% CI, 12.3 to
18.9 months), respectively. The most common toxicities were
myelosuppression (leukopenia, neutropenia, and thrombocytopenia) and
elevated liver enzymes. Pseudoprogression was observed in 37% of
assessable patients and may have had an impact on estimates of
progression-free survival (6.6 months in the dose-dense arm and 5.0
months in the metronomic arm).
CONCLUSION: Both dose-dense and
metronomic temozolomide regimens were well tolerated with modest
toxicity. The dose-dense regimen appears promising, with 1-year
survival of 80%.