Concurrent whole brain radiotherapy and bortezomib for brain metastasis

Radiation Oncology

Bruce G Redman³  James Hayman¹  Theodore Lawrence¹  Daniel Hamstra¹  Catherine Van Poznak³  Matt Schipper¹  Oliver Lee¹  Yue Cao²  Christopher Chapman¹  Daniel P Normolle⁵  Christina I Tsien¹  Judah Friedman⁴  Christopher D Lao³ 

[1] Radiation Oncology, University of Michigan, Ann Arbor, MI, USA;Radiology, University of Michigan, Ann Arbor, MI, USA;Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor 48109-0848, MI, USA;University Hospitals, Cleveland, OH, USA;Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA

关键词: MRI;    Diffusion tensor imaging;    TITE-CRM;    Phase I;    Bortezomib;    Melanoma;    Brain;    Radiation;   

Others  :  1153126
DOI  :  10.1186/1748-717X-8-204

 received in 2013-03-25, accepted in 2013-08-16,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Lao et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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