Originally published as JCO Early Release 10.1200/JCO.2008.19.3789 on May 18 2009

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Google Scholar Articles by Angelov, L. Articles by Neuwelt, E. A. PubMed PubMed Citation Articles by Angelov, L. Articles by Neuwelt, E. A. Social Bookmarking                            What's this?

Blood-Brain Barrier Disruption and Intra-Arterial Methotrexate-Based Therapy for Newly Diagnosed Primary CNS Lymphoma: A Multi-Institutional Experience

From the Brain Tumor and Neuro-Oncology Center and Departments of Neurosurgery and Hematology and Medical Oncology, Cleveland Clinic, Cleveland; Department of Neurosurgery, Ohio State University Medical Center, Columbus, OH; Departments of Neurology, Public Health and Preventive Medicine, Department of Medical Informatics and Clinical Epidemiology, Medicine, and Neurosurgery, Oregon Health & Science University; Department of Pharmacy Practice, Oregon State University; Portland Veterans Affairs Medical Center, Portland, OR; and Leslie and Michael Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel.

Corresponding author: Edward A. Neuwelt, MD, 3181 SW Sam Jackson Park Rd, Mailcode L603, Portland, OR 97239; e-mail: neuwelte{at}ohsu.edu.

Purpose Primary CNS lymphoma (PCNSL) is confined to the CNS and/or the eyes at presentation and is usually initially treated with intravenous methotrexate-based chemotherapy and whole-brain radiotherapy (WBRT). However, the intact blood-brain barrier (BBB) can limit diffusion of methotrexate into brain and tumor. With BBB disruption (BBBD), enhanced drug delivery to the tumor can be achieved.

Patients and Methods This report summarizes the multi-institutional experience of 149 newly diagnosed (with no prior WBRT) patients with PCNSL treated with osmotic BBBD and intra-arterial (IA) methotrexate at four institutions from 1982 to 2005. In this series, 47.6% of patients were age 60 years, and 42.3% had Karnofsky performance score (KPS) less than 70 at diagnosis.

Results The overall response rate was 81.9% (57.8% complete; 24.2% partial). Median overall survival (OS) was 3.1 years (25% estimated survival at 8.5 years). Median progression-free survival (PFS) was 1.8 years, with 5-year PFS of 31% and 7-year PFS of 25%. In low-risk patients (age < 60 years and KPS 70), median OS was approximately 14 years, with a plateau after approximately 8 years. Procedures were generally well tolerated; focal seizures (9.2%) were the most frequent side effect and lacked long-term sequelae.

Conclusion This large series of patients treated over a 23-year period demonstrates that BBBD/IA methotrexate-based chemotherapy results in successful and durable tumor control and outcomes that are comparable or superior to other PCNSL treatment regimens.

Supported by a Veterans Administration Merit Review Grant and National Institutes of Health Grants No. CA137488, NS34608, and NS44687 from the National Cancer Institute and the National Institute of Neurological Disorders and Stroke to E.A.N.

Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 3, 2007, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?