Continuous tamoxifen and dose-dense temozolomide in recurrent glioblastoma

The current standard-of-care for glioblastoma (GBM) is represented by concomitant radiotherapy (RT) and temozolomide (TMZ), according to Stupp's protocol. Second-line treatments for GBM have not been yet defined. Tamoxifen is an anti-estrogen molecule with anti-neoplastic effects whose role is under investigation. tamoxifen is generally well tolerated but thromboembolic complications have been reported. In this study, we report our experience on the administration of tamoxifen plus dose-dense TMZ in patients with recurrent GBM.

All patients underwent surgical resection of GBM and completed concomitant RT and TMZ. Eligibility criteria also included evidence of GBM recurrence and good general conditions [Karnofsky Performance Score (KPS) >70] at recurrence. Patients with rapidly progressive disease, clearly unfavorable prognosis, or history of deep-venous thrombosis were excluded. The second-line treatment consisted of dose-dense TMZ (75-150 mg/m(2) one week on/ one week off) plus daily tamoxifen (80 mg/m(2)). Follow-up was performed with contrast-enhanced brain Magnetic Resonance Imaging (MRI) every three months.

Thirty-two patients (18 males, 14 females; median age 57 years) with GBM relapse were included. Median overall survival time (OS) and time to tumor progression after recurrence (TTP-2) were 17.5 and 7 months, respectively. Interestingly, no differences in OS and TTP-2 were noted in GBM between those with methylated and unmethylated MGMT. None of the patients had complications related to TMZ plus tamoxifen administration.

The combinatorial administration of tamoxifen and TMZ appeared to be well-tolerated, and potentially effective in increasing the efficacy of dose-dense TMZ schedule as a second-line therapeutic strategy.