Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points

Minesh P. Mehta, William R. Shapiro, Michael Glantz, Roy A. Patchell, Michael A. Weitzner, Christina A. Meyers, Christopher J. Schultz, Wilson H. Roa, Mark Leibenhaut, Judith Ford, Walter Curran, See Phan, Jennifer A. Smith, Richard A. Miller, Markus F. Renschler

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Purpose: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases. Patients and Methods: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points. Results: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium's tumor selectivity was established with MRI. Conclusion: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.

Original languageEnglish (US)
Pages (from-to)3445-3453
Number of pages9
JournalJournal of Clinical Oncology
Volume20
Issue number16
DOIs
StatePublished - Aug 15 2002

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Nervous System
Magnetic Resonance Imaging
Radiation
Neoplasm Metastasis
Brain
Radiotherapy
Neurologic Examination
Oxidation-Reduction
motexafin gadolinium
Cause of Death
Neoplasms
Breast Neoplasms
Safety
Lung
Survival
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Mehta, Minesh P. ; Shapiro, William R. ; Glantz, Michael ; Patchell, Roy A. ; Weitzner, Michael A. ; Meyers, Christina A. ; Schultz, Christopher J. ; Roa, Wilson H. ; Leibenhaut, Mark ; Ford, Judith ; Curran, Walter ; Phan, See ; Smith, Jennifer A. ; Miller, Richard A. ; Renschler, Markus F. / Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases : Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. In: Journal of Clinical Oncology. 2002 ; Vol. 20, No. 16. pp. 3445-3453.
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title = "Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points",
abstract = "Purpose: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases. Patients and Methods: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points. Results: Twenty-five patients with brain metastases from lung (52{\%}) and breast (24{\%}) cancer, recursive partitioning analysis class 2 (96{\%}), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77{\%} at 1 year. Median survival was 5.0 months. In 29{\%} of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68{\%}. Motexafin gadolinium's tumor selectivity was established with MRI. Conclusion: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.",
author = "Mehta, {Minesh P.} and Shapiro, {William R.} and Michael Glantz and Patchell, {Roy A.} and Weitzner, {Michael A.} and Meyers, {Christina A.} and Schultz, {Christopher J.} and Roa, {Wilson H.} and Mark Leibenhaut and Judith Ford and Walter Curran and See Phan and Smith, {Jennifer A.} and Miller, {Richard A.} and Renschler, {Markus F.}",
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Mehta, MP, Shapiro, WR, Glantz, M, Patchell, RA, Weitzner, MA, Meyers, CA, Schultz, CJ, Roa, WH, Leibenhaut, M, Ford, J, Curran, W, Phan, S, Smith, JA, Miller, RA & Renschler, MF 2002, 'Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points', Journal of Clinical Oncology, vol. 20, no. 16, pp. 3445-3453. https://doi.org/10.1200/JCO.2002.07.500

Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases : Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. / Mehta, Minesh P.; Shapiro, William R.; Glantz, Michael; Patchell, Roy A.; Weitzner, Michael A.; Meyers, Christina A.; Schultz, Christopher J.; Roa, Wilson H.; Leibenhaut, Mark; Ford, Judith; Curran, Walter; Phan, See; Smith, Jennifer A.; Miller, Richard A.; Renschler, Markus F.

In: Journal of Clinical Oncology, Vol. 20, No. 16, 15.08.2002, p. 3445-3453.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases

T2 - Centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points

AU - Mehta, Minesh P.

AU - Shapiro, William R.

AU - Glantz, Michael

AU - Patchell, Roy A.

AU - Weitzner, Michael A.

AU - Meyers, Christina A.

AU - Schultz, Christopher J.

AU - Roa, Wilson H.

AU - Leibenhaut, Mark

AU - Ford, Judith

AU - Curran, Walter

AU - Phan, See

AU - Smith, Jennifer A.

AU - Miller, Richard A.

AU - Renschler, Markus F.

PY - 2002/8/15

Y1 - 2002/8/15

N2 - Purpose: Motexafin gadolinium is a redox mediator that selectively targets tumor cells, is detectable by magnetic resonance imaging (MRI), and enhances the effect of radiation therapy. This lead-in phase to a randomized trial served to evaluate radiologic, neurocognitive, and neurologic progression end points and to evaluate the safety and radiologic response of motexafin gadolinium administered concurrently with 30 Gy in 10-fraction whole-brain radiation therapy for the treatment of brain metastases. Patients and Methods: Motexafin gadolinium (5.0 mg/kg/d for 10 days) was administered before each radiation treatment in this prospective international trial. Patients were evaluated by MRI, neurologic examinations, and neurocognitive tests. Prospective criteria and centralized review procedures were established for radiologic, neurocognitive, and neurologic progression end points. Results: Twenty-five patients with brain metastases from lung (52%) and breast (24%) cancer, recursive partitioning analysis class 2 (96%), and an average of 11 brain metastases were enrolled. Neurocognitive function was highly impaired at presentation. Motexafin gadolinium was well tolerated. Freedom from neurologic progression was 77% at 1 year. Median survival was 5.0 months. In 29% of patients, the cause of death was brain metastasis progression. The radiologic response rate was 68%. Motexafin gadolinium's tumor selectivity was established with MRI. Conclusion: (1) Centralized neurologic progression scoring that incorporated neurocognitive tests was implemented successfully. (2) Motexafin gadolinium was well tolerated. (3) Local control, measured by radiologic response rate, neurologic progression, and death caused by progression of brain metastasis, seemed to be improved compared with historical results. A randomized phase III trial using these methods for evaluation of efficacy has just been completed.

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