title: Treatment of recurrent glioblastoma: can local delivery of mitoxantrone improve survival?
abstract: In this study, the records of 276 adult patients with recurrent glioblastoma (GBM) treated at recurrence at our institution between 2004 and 2006 were reviewed for progression-free survival (PFS), overall survival (OS), and toxicity. At recurrence, all patients underwent systemic treatment with temozolomide (200 mg/sqm on days 1-5 every 28 days) until tumor progression. Patients, whose tumor was judged resectable without risk of adjunctive neurological deficit, underwent a second surgery with or without positioning of a Rickam/Ommaya reservoir. The reservoir was used for locoregional chemotherapy with mitoxantrone. Two hundred seventy-six rGBL patients (pts) were divided into three subgroups: A 161 pts treated only with temozolomide, B 50 pts re-operated-on +temozolomide, and C 65 pts re-operated on + temozolomide + locoregional CHT. For group A, the 6 month PFS and 6 month survival (ST) were 39.3 and 43%, respectively, with a median survival time (mST) of 5 months (range 4-6) and 25% of pts alive at 9 months. For group B, the 6 month PFS and 6 month survivors were 64 and 74.1%, respectively, with a mST of 8 months (range 6-10) and 25% of pts alive at 12 months. For group C, the 6 month PFS and 6 month survivors were 70.7 and 87.7%, respectively, with a mST of 11 months (range 9-13) and 25% of pts alive at 18 months (A vs. B vs. C, log-rank P < 0.001) (B vs. C, P = 0.041) (A vs. B P = 0.009). Cox proportional hazard model was used to obtain Hazard Ratio (HR) for type of treatment corrected by age and time (in months) between diagnosis and first recurrence: second tumor debulking was statistically effective for survival, reducing by 36% the risk of death (HR = 0.64; 0.46-0.89), but the most significant favorable prognostic factor for survival was the local delivery of mitoxantrone which reduced the risk of death to 50% (HR = 0.50; 0.38-0.68).
authors.affiliation: Department of Neuro-oncology, Fondazione IRCSS Istituto Neurologico Carlo Besta, Via Celoria 11, Milan, Italy. boiardi@istituto-besta.it
authors.forename: Amerigo
authors.initials: A
authors.lastname: Boiardi
authors.forename: Antonio
authors.initials: A
authors.lastname: Silvani
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.forename: Elena
authors.initials: E
authors.lastname: Lamperti
authors.forename: Andrea
authors.initials: A
authors.lastname: Salmaggi
authors.forename: Paola
authors.initials: P
authors.lastname: Gaviani
authors.forename: Anna
authors.initials: A
authors.lastname: Fiumani
authors.forename: Andrea
authors.initials: A
authors.lastname: Botturi
authors.forename: Chiara
authors.initials: C
authors.lastname: Falcone
authors.forename: Alessandra
authors.initials: A
authors.lastname: Solari
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Meco
authors.forename: Giovanni
authors.initials: G
authors.lastname: Broggi
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local; D019635:Neurosurgical Procedures; D049268:Positron-Emission Tomography; D012189:Retrospective Studies; D013534:Survival; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D008942:Mitoxantrone; D000077204:Temozolomide