The Pathophysiology of Bortezomib Induced Peripheral Neuropathy

NCT ID: NCT01171443

Last Updated: 2010-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-08-31

Brief 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.

Detailed 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.

Conditions

Multiple Myeloma

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

1. A total of 30 newly diagnosed patients (age > 18 years) with multiple myeloma (stage3 Durie and Salmon, ECOG-performance status <2), who are candidates for bortezomib therapy will be enrolled in the study (duration of the study 6 months).

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wolfson Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

hematology department on Wolfsson Medical Center

Principal Investigators

GHOTI HOSSAM

Role: PRINCIPAL_INVESTIGATOR

HEMATOLOGY DEPARTMENT ON WOLFSSON MEDICAL CENTER

Locations

Wolfsson Medical Center

Holon, Israel, Israel

Countries

Israel

Central Contacts

Ghoti Hossam

Role: CONTACT

drghoti123@yahoo.com

035028110

Facility Contacts

GHOTI HOSSAM

Role: primary

drghoti123@yahoo.com

970-35028110

Other Identifiers

0102-10CTIL

Identifier Type: -

Identifier Source: org_study_id