Concurrent Bortezomib Research Articles

Unilateral Cervical Polyneuropathies following Concurrent Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer.

We report a constellation of cervical polyneuropathies in a patient treated with concurrent bortezomib, cetuximab, and cisplatin alongside intensity modulated radiotherapy for carcinoma of the tonsil with neck metastasis. The described deficits include brachial plexopathy, cervical sensory neuropathy, and oculosympathetic, recurrent laryngeal, and phrenic nerve palsies within the ipsilateral radiation field. Radiation neuropathy involving the brachial plexus is typically associated with treatment of breast or lung cancer; however, increased awareness of this entity in the context of investigational agents with potential neuropathic effects in head and neck cancer has recently emerged. With this report, we highlight radiation neuropathy in the setting of investigational therapy for head and neck cancer, particularly since these sequelae may present years after therapy and entail significant and often irreversible morbidity.

Plasmablastic Lymphoma of the Maxillary Sinus: Case Report of a Novel Treatment Approach of Concurrent Bortezomib and Intensity-Modulated Radiotherapy

Plasmablastic lymphoma (PBL) is an aggressive variant of diffuse large B-cell lymphoma and was initially described as affecting the oral cavity of patients with HIV. Recently, it has been better characterized through histopathology and case reports demonstrating that it may affect HIV-negative patients as well. In particular, elderly patients that have immunosenescence can develop PBL, and it may present in anatomic sites outside the oral cavity. Treatment typically consists of aggressive chemotherapy regimens, such as CHOP, EPOCH, or hyperCVAD; however, elderly patients may not be able to tolerate such intense regimens. We present a case of an elderly man with PBL of the maxillary sinus treated with a unique regimen of concurrent bortezomib and intensity-modulated radiotherapy (IMRT). This treatment produced a significant, durable tumor response and was well tolerated. Bortezomib with IMRT could be considered an alternative to more intense chemotherapy regimens, particularly in elderly patients with PBL, although prospective studies are needed to further test the safety and efficacy.

Concurrent whole brain radiotherapy and bortezomib for brain metastasis

BackgroundSurvival 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.MethodsA 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.ResultsTwenty-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).ConclusionsConcurrent 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.

Proteasome inhibition attenuates angiotensin II‐induced hypertension and vascular remodeling

Growing evidence implicates the proteasome in cardiovascular disease. However, its role in hypertension is understudied. Accordingly, this study tested the hypothesis that proteasome inhibition attenuates hypertension development and related vascular remodeling.Male Sprague Dawley rats were given chronic subcutaneous infusion of angiotensin II (AngII) to induce hypertension or vehicle infusion for 2 weeks. The rats were concurrently treated with a proteasome inhibitor, bortezomib (200 μg/kg 3 times per week). Arterial blood pressure was measured from conscious rats via indwelling catheters. After euthanasia the aorta and tibialis anterior skeletal muscle were collected. Histochemical (Masson's Trichrome) and immunohistochemical (CD31) staining were used to estimate wall to lumen ratio and capillary density respectively.Compared to vehicle (131±7 mm Hg), Ang II infusion caused a marked increase in arterial pressure (159±4 mm Hg). Aortic wall to lumen ratio was increased (+20%) whereas capillary density in skeletal muscle was reduced (−30%). Concurrent bortezomib treatment markedly attenuated these responses (arterial pressure 138±5 mm Hg, aorta wall to lumen ratio −1%, capillary density −8%).Collectively, these data suggest that inhibition of the proteasome attenuated Ang II hypertension development and related vascular remodeling. Supported by NIH #2RO1HL63053‐ARRA (DM).

HHV-8–Associated Multicentric Castleman's Disease in HIV-Negative Patient: A Novel Therapy for an Orphan Disease

A case of multicentric Castleman's disease in an HIV− human herpesvirus 8+ patient who was successfully managed with concurrent bortezomib and ganciclovir is presented.

Phase I Trial of Concurrent Bortezomib, Paclitaxel, and External Beam Radiation in Patients with Unresectable Pancreatic or Billiary Cancer

Phase I Trial of Concurrent Bortezomib, Paclitaxel, and External Beam Radiation in Patients with Unresectable Pancreatic or Billiary Cancer

Severe Acute Enteritis in a Multiple Myeloma Patient Receiving Bortezomib and Spinal Radiotherapy: Case Report

Proteasome inhibitors have been reported to enhance radiosensitivity in vitro. A case of potential clinical interaction between bortezomib, a proteasome inhibitor, and spine radiation is reported. A woman undergoing palliative radiotherapy to the T12 -S2 spine with concurrent bortezomib developed unexpectedly severe, acute radiation enteritis requiring hospital admission. Clinicians are advised to consider the potential for interactions of bortezomib with radiotherapy when the two agents are used simultaneously in the clinic.