title: Intra-arterial carboplatin as a salvage strategy in the treatment of recurrent glioblastoma multiforme.
abstract: The first-line treatment of glioblastoma typically consists of a maximal surgical resection, followed by a combination of radio-chemotherapy with temozolomide. There is however no consensus regarding optimal therapeutic approaches at relapse. The following phase II study explored the therapeutic gain obtained when exposing these patients to a combination of intra-arterially administered carboplatin and melphalan at first or second relapse as a salvage treatment in recurrent glioblastoma. Fifty-one consecutive patients diagnosed with glioblastoma were accrued and offered this treatment at first or second relapse. A Karnofsky score of ≥ 60 was required, and when appropriate, patients were first reoperated prior to accrual. Patients enrolled were treated every 4 weeks (1 cycle) for up to 12 cycles. Progression was evaluated by Macdonald criteria. Primary end point surrogates were overall survival from diagnosis and study entry. Median survival from diagnosis and study entry was 23 and 11 months, respectively. The median time to progression was 5.2 months. All patients enrolled were treated for a minimum of 2 cycles. Hematologic toxicity was manageable, with an 8 % of grade II neutropenia, 12 % of grade II thrombocytopenia and 7 % of grade III thrombocytopenia. This therapeutic strategy represents an adequate option in the second-line treatment of recurrent glioblastoma. The adjunction of an osmotic permeabilization could be considered to further expand delivery, and hopefully improve survival in these patients.
authors.affiliation: Division of Neurosurgery and Neuro-Oncology, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, J1H 5N4, Canada, david.fortin@usherbrooke.ca.
authors.forename: David
authors.initials: D
authors.lastname: Fortin
authors.forename: Pierre-Aurèle
authors.initials: PA
authors.lastname: Morin
authors.forename: Francois
authors.initials: F
authors.lastname: Belzile
authors.forename: David
authors.initials: D
authors.lastname: Mathieu
authors.forename: Francois-Michel
authors.initials: FM
authors.lastname: Paré
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin