Clinical trial NCT01171443: The Pathophysiology of Bortezomib Induced Peripheral Neuropathy
Official title: Is There a Role of Oxidative Stress in the Pathophysiology of Bortezomib Induced Peripheral Neuropathy (BIPN) in Multiple Myeloma Patients?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Myeloma
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2010-07-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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).

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Holon
country: Israel
facility: Wolfsson Medical Center
Study officials:
affiliation: HEMATOLOGY DEPARTMENT ON WOLFSSON MEDICAL CENTER
name: GHOTI HOSSAM
role: PRINCIPAL_INVESTIGATOR
References: