However, these side effects are usually mild relative to bone marrow transplantation and other treatment options for patients with advanced disease.Bortezomib is associated with a high rate of shingles, (with or without dexamethasone) administered by intravenous bolus on days 1,4,8, and 11 of a 21-day cycle for a maximum of eight cycles in heavily pretreated patients with relapsed/refractory multiple myeloma.
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The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity.
In normal cells, the proteasome regulates protein expression and function by degradation of ubiquitylated proteins, and also cleanses the cell of abnormal or misfolded proteins.
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Recently, it was found that bortezomib caused a rapid and dramatic change in the levels of intracellular peptides that are produced by the proteasome.
Some intracellular peptides have been shown to be biologically active, and so the effect of bortezomib on the levels of intracellular peptides may contribute to the biological and/or side effects of the drug.
Pharmacodynamics are measured by measuring proteasome inhibition in peripheral blood mononuclear cells.
The much greater sensitivity of myeloma cell lines and mantle cell lines to proteasome inhibition compared with normal peripheral blood mononuclear cells and most other cancer cell lines is poorly understood.
This can be worse in patients with pre-existing neuropathy.