The Pathophysiology of Bortezomib Induced Peripheral Neuropathy

Last updated: July 27, 2010
Sponsor: Wolfson Medical Center
Overall Status: Trial Status Unknown

Phase

N/A

Condition

Multiple Myeloma

Cancer

Lymphoproliferative Disorders

Treatment

N/A

Clinical Study ID

NCT01171443
0102-10CTIL
  • Ages > 18
  • All Genders

Study Summary

Since the pathophysiology of BIPN still remains unclear, in the present study we are going to assess the development of BIPN in newly diagnosed myeloma patients, based on clinical neurological examination and electrophysiological study (EMG) and trying to find out if there is any relationship between oxidative stress generation measured by serum malonyldialdehyde - (MDA) and urinary isoprostane, and the development of BIPN, which can explain important part of the BIPN pathophysiology and can suggest new ideas of treatment and prophylactic strategies of peripheral neuropathy.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. A total of 30 newly diagnosed patients (age > 18 years) with multiple myeloma (stage3Durie and Salmon, ECOG-performance status <2), who are candidates for bortezomibtherapy will be enrolled in the study (duration of the study 6 months).

Exclusion

Exclusion Criteria:

  1. Patients with relapsed or progressive multiple myeloma.

  2. Performance status > 2.

  3. Prior treatment with neuropathic agents such as Oncovin and thalidomide.

Study Design

Total Participants: 30
Study Start date:
August 01, 2010
Estimated Completion Date:
August 31, 2011

Study Description

The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in combination with other novel agents for the treatment of multiple myeloma (MM).

Peripheral neuropathy is a significant dose limiting toxicity of bortezomib, which typically occurs within the first treatment cycles with bortezomib, reaching plateau around cycle 5, and does not appear to increase thereafter.

Although bortezomib is known to be selective proteasome inhibitor, the mechanisms of cytotoxicity are poorly understood.

It has been theoretically hypothesized that bortezomib abrogates the degradation of I-kB, which blocks the transcriptional activity of NF-kB, however, recent studies demonstrated that bortezomib elicits activation of multiple pathways in cancer cells, such as reactive oxygen species (ROS) pathway.

The involvement of oxidative stress is supported by emerging studies showing that ROS generation plays a critical role in the initiation of the bortezomib induced apoptotic cascade.

Oxidative stress is a complex and dynamic situation characterized by an imbalance between the productions of ROS and the availability and action of antioxidants.

Connect with a study center

  • Wolfsson Medical Center

    Holon,
    Israel

    Site Not Available

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