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

Research output: Contribution to journalArticle

282 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 (US)
Pages (from-to)637-647
Number of pages11
JournalCancer
Volume88
Issue number3
DOIs
StatePublished - Feb 1 2000

Fingerprint

Blood-Brain Barrier
Brain Neoplasms
Multicenter Studies
Germ Cell and Embryonal Neoplasms
Safety
Drug Therapy
Primitive Neuroectodermal Tumors
Central Nervous System
Lymphoma
Therapeutics
Glioma
Guidelines
Neoplasm Metastasis
Karnofsky Performance Status
Brain
Glioblastoma
Tears
Pulmonary Embolism
Catheterization
Nervous System

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Cancer, Vol. 88, No. 3, 01.02.2000, p. 637-647.

Research output: Contribution to journalArticle

Doolittle, Nancy ; Miner, Michael E. ; Hall, Walter A. ; Siegal, Tali ; Hanson, E. Jerome ; Osztie, Eva ; McAllister, Leslie D. ; Bubalo, Joseph ; Kraemer, Dale ; Fortin, David ; Nixon, Randal ; Muldoon, Leslie ; Neuwelt, Edward. / 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. In: Cancer. 2000 ; Vol. 88, No. 3. pp. 637-647.
@article{c4dbd5e7c8364c8c8fea5cc62baff695,
title = "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",
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.",
keywords = "Blood-brain barrier, Brain tumors, Intraarterial chemotherapy, Neuro-oncology",
author = "Nancy Doolittle and Miner, {Michael E.} and Hall, {Walter A.} and Tali Siegal and Hanson, {E. Jerome} and Eva Osztie and McAllister, {Leslie D.} and Joseph Bubalo and Dale Kraemer and David Fortin and Randal Nixon and Leslie Muldoon and Edward Neuwelt",
year = "2000",
month = "2",
day = "1",
doi = "10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y",
language = "English (US)",
volume = "88",
pages = "637--647",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - 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

AU - Doolittle, Nancy

AU - Miner, Michael E.

AU - Hall, Walter A.

AU - Siegal, Tali

AU - Hanson, E. Jerome

AU - Osztie, Eva

AU - McAllister, Leslie D.

AU - Bubalo, Joseph

AU - Kraemer, Dale

AU - Fortin, David

AU - Nixon, Randal

AU - Muldoon, Leslie

AU - Neuwelt, Edward

PY - 2000/2/1

Y1 - 2000/2/1

N2 - 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.

AB - 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.

KW - Blood-brain barrier

KW - Brain tumors

KW - Intraarterial chemotherapy

KW - Neuro-oncology

UR - http://www.scopus.com/inward/record.url?scp=0034142246&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034142246&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y

DO - 10.1002/(SICI)1097-0142(20000201)88:3<637::AID-CNCR22>3.0.CO;2-Y

M3 - Article

C2 - 10649259

AN - SCOPUS:0034142246

VL - 88

SP - 637

EP - 647

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 3

ER -