title: Continuous tamoxifen and dose-dense temozolomide in recurrent glioblastoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurosurgery, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico - 22, F. Sforza street, Milan 20122, Italy. andrea.dicristofori@gmail.com
authors.forename: Andrea
authors.initials: A
authors.lastname: DI Cristofori
authors.forename: Giorgio
authors.initials: G
authors.lastname: Carrabba
authors.forename: Giordano
authors.initials: G
authors.lastname: Lanfranchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Menghetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Rampini
authors.forename: Manuela
authors.initials: M
authors.lastname: Caroli
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide
keywords: Glioblastoma; dose-dense schedule; tamoxifen; temozolomide