Even after gross
tumor resection and combined
radiochemotherapy,
glioblastomas recur within a few months.
Salvage therapy often consists of rechallenging with
temozolomide in a dose-intensified schedule. Previously, low-dose metronomic
temozolomide in combination with cyclo-oxigenase 2 inhibitors has had a beneficial effect as first-line treatment for
glioblastoma. We report our experience with this procedure in recurrent
glioblastomas after standard treatment. From June 2007 to April 2009, 28 patients with recurrent
glioblastoma received continuous low-dose
temozolomide of 10 mg/m(2) twice daily and 200 mg
celecoxib. Before
therapy the recurrent
tumor was resected in 19 of 28 patients. Microvessel density (MVD) was determined by immunohistochemistry in 19 patients, and MGMT promoter methylation status, using the pyrosequencing method, was determined in 17 patients. In 14/28 patients, positron emission tomography with [F-18]-fluoroethyl)-
L-tyrosine (FET-PET) was performed.
Tumor progression was defined by the Macdonald criteria on MRI every 8-12 weeks or by
clinical deterioration. The median time to progression was 4.2 months. Progression-free survival (PFS) after 6 months was 43%. Except for a
lymphopenia in one patient, there was no grade 3 or 4 toxicity. PFS did not correlate with MVD or MGMT status. A high FET uptake correlated with
tumor control after 6 months under
therapy (P = 0.041, t-test). Low-dose continuous
temozolomide in combination with
celecoxib seems to have activity in recurrent
glioblastoma without relevant toxicity. High FET uptake correlated with a better outcome under metronomic
therapy.