title: Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma.
abstract: Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.
authors.affiliation: Department of Neurology, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Carpentier
authors.forename: Florence
authors.initials: F
authors.lastname: Laigle-Donadey
authors.forename: Sarah
authors.initials: S
authors.lastname: Zohar
authors.forename: Laurent
authors.initials: L
authors.lastname: Capelle
authors.forename: Anthony
authors.initials: A
authors.lastname: Behin
authors.forename: Annick
authors.initials: A
authors.lastname: Tibi
authors.forename: Nadine
authors.initials: N
authors.lastname: Martin-Duverneuil
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Sophie
authors.initials: S
authors.lastname: Taillibert
authors.forename: Louis
authors.initials: L
authors.lastname: Puybasset
authors.forename: Remy
authors.initials: R
authors.lastname: Van Effenterre
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
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; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides