QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carpentier, A. Articles by Carpentier, A. F. Search for Related Content PubMed PubMed Citation

Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma¹

Departments of Neurosurgery (A.C., L.C., R.V), Neurology Mazarin (F.L.-D., A.B., M. S., L.L., S.T., J-Y.D., A.F.C.), Anesthesia (L.P.), and Neuroradiology (N.M-D.), Hôpital de la Salpêtrière, Paris; Department of Biostatistics, Hôpital Saint-Louis, Paris (S.Z.); and Agence Générale des Equipements et Produits de Santé, Paris (A.T.); France

² Address correspondence to Antoine F. carpentier, Department of Neurology Mazarin, 47 boulevard de l'Hôpital, Hôpital de la Salpêtrière, 75013 Paris, France (antoine.carpentier{at}psl.ap-hopparis.fr).

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°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.

Key Words: convection-enhanced delivery • CpG ODN • glioblastoma • glioma • immunotherapy • oligodeoxynucleotide • phase 1

This article has been cited by other articles:

				O. M. Grauer, J. W. Molling, E. Bennink, L. W. J. Toonen, R. P. M. Sutmuller, S. Nierkens, and G. J. Adema TLR Ligands in the Local Treatment of Established Intracerebral Murine Gliomas J. Immunol., November 15, 2008; 181(10): 6720 - 6729. [Abstract] [Full Text] [PDF]

				Z. Xiong, S. Gharagozlou, I. Vengco, W. Chen, and J. R. Ohlfest Effective CpG Immunotherapy of Breast Carcinoma Prevents but Fails to Eradicate Established Brain Metastasis Clin. Cancer Res., September 1, 2008; 14(17): 5484 - 5493. [Abstract] [Full Text] [PDF]

				M. T. Krauze, C. O. Noble, T. Kawaguchi, D. Drummond, D. B. Kirpotin, Y. Yamashita, E. Kullberg, J. Forsayeth, J. W. Park, and K. S. Bankiewicz Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts Neuro-oncol, October 1, 2007; 9(4): 393 - 403. [Abstract] [Full Text] [PDF]