title: Intracerebral injection of CpG oligonucleotide for patients with de novo glioblastoma-A phase II multicentric, randomised study.
abstract: Immunostimulating oligodeoxynucleotides containing unmethylated cytosine-guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas.
  
  
  
  Patients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance.
  
  
  
  Eighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm.
  
  
  
  Local immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed GBM.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service de Neurologie, Bobigny, France. Electronic address: renata.ursu@aphp.fr.
authors.forename: Renata
authors.initials: R
authors.lastname: Ursu
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Pitie Salpetriere Hospital, Department of Neurosurgery, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Carpentier
authors.affiliation: Department of Neurosurgery, CHU Timone, Marseille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Metellus
authors.affiliation: Department of Neurosurgery, Centre Hospitalier Universitaire, Toulouse, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lubrano
authors.affiliation: Assistance Publique-Hopitaux de Paris, Department of Neurology Mazarin, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Laigle-Donadey
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Pitie Salpetriere Hospital, Department of Neurosurgery, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Capelle
authors.affiliation: Neurosurgical Department D, Neurological Hospital, Lyon, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Guyotat
authors.affiliation: Department of Neurosurgery, CHU Charles-Nicolle, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Langlois
authors.affiliation: Department of Neurosurgery, CHU Gui de Chauliac, Montpellier, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Bauchet
authors.affiliation: Department of Biostatistics, Hospital Saint-Louis, Paris, France.
authors.forename: Kristell
authors.initials: K
authors.lastname: Desseaux
authors.affiliation: Agence Générale des Equipements et Produits de Santé (AGEPS), Paris, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Tibi
authors.affiliation: Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Department of Neuro-Oncology, CHU Timone, Marseille, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Chinot
authors.affiliation: Department of Biostatistics, Hospital Saint-Louis, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Service de Neurologie, Bobigny, France; Université Paris 13, UFR de Santé, Médecine et Biologie Humaine, Bobigny, France.
authors.forename: Antoine F
authors.initials: AF
authors.lastname: Carpentier
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D016037:Single-Blind Method; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D018906:Antineoplastic Agents, Alkylating; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9
keywords: CpG-28; CpG-ODN; Glioblastoma; Phase II; TLR9