Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors

Nancy D. Doolittle, Michael E. Miner, Walter A. Hall, Tali Siegal, E. Jerome Hanson, Eva Osztie, Leslie D. McAllister, Joseph S. Bubalo, Dale F. Kraemer, David Fortin, Randal Nixon, Leslie L. Muldoon, Edward A. Neuwelt

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289 Citations (Scopus)

Abstract

BACKGROUND. The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood- brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers. METHODS. Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures). RESULTS. Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment. CONCLUSIONS. Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy- sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.

Original languageEnglish
Pages (from-to)637-647
Number of pages11
JournalCancer
Volume88
Issue number3
DOIs
Publication statusPublished - Feb 1 2000

Keywords

  • Blood-brain barrier
  • Brain tumors
  • Intraarterial chemotherapy
  • Neuro-oncology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Doolittle, N. D., Miner, M. E., Hall, W. A., Siegal, T., Hanson, E. J., Osztie, E., McAllister, L. D., Bubalo, J. S., Kraemer, D. F., Fortin, D., Nixon, R., Muldoon, L. L., & Neuwelt, E. A. (2000). Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood-brain barrier for the treatment of patients with malignant brain tumors. Cancer, 88(3), 637-647. https://doi.org/10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y