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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 MP, Shapiro WR, Glantz MJ, Patchell RA, Weitzner MA, Meyers CA, Schultz
CJ, Roa WH, Leibenhaut M, Ford J, Curran W, Phan S, Smith JA, Miller RA,
Renschler MF
Department of Human Oncology, Medical School, University of
Wisconsin-Madison, K4/334 Clinical Science Center, 600 Highland Avenue, Madison,
WI 53792, USA. mehta@mail.humonc.wisc.edu
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.
PMID: 12177105 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12177105&dopt=Abstract |
