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Concurrent whole brain radiotherapy and bortezomib for brain metastasis

Lao, CD and Friedman, J and Tsien, CI and Normolle, DP and Chapman, C and Cao, Y and Lee, O and Schipper, M and Van Poznak, C and Hamstra, D and Lawrence, T and Hayman, J and Redman, BG (2013) Concurrent whole brain radiotherapy and bortezomib for brain metastasis. Radiation Oncology, 8 (1).

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Abstract

Background: Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis.Methods: A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects.Results: Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023).Conclusions: Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment. © 2013 Lao et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lao, CD
Friedman, J
Tsien, CI
Normolle, DPdpn7@pitt.eduDPN70000-0001-8675-5014
Chapman, C
Cao, Y
Lee, O
Schipper, M
Van Poznak, C
Hamstra, D
Lawrence, T
Hayman, J
Redman, BG
Date: 21 August 2013
Date Type: Publication
Journal or Publication Title: Radiation Oncology
Volume: 8
Number: 1
DOI or Unique Handle: 10.1186/1748-717x-8-204
Schools and Programs: Graduate School of Public Health > Biostatistics
Refereed: Yes
Date Deposited: 02 Dec 2016 14:59
Last Modified: 02 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/29692

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