Bortezomib

bortezomib

(bor-TEH-zoh-mib)

A drug used to treat multiple myeloma. It is also used to treat mantle cell lymphoma in patients who have already received at least one other type of treatment and is being studied in the treatment of other types of cancer. Bortezomib blocks several molecular pathways in a cell and may cause cancer cells to die. It is a type of proteasome inhibitor and a type of dipeptidyl boronic acid. Also called PS-341 and Velcade.

Mechanism of action of Bortezomib

Bortezomib (bor tez’ oh mib) is an orally available, small molecule inhibitor of the 26S proteasome, the intracellular complex that degrades proteins involved in cell signaling and cell cycle regulation. Blocking proteasome activity prevents activation of factors involved in cell growth and resistance to chemotherapy induced apoptosis, leading to cancer cell death. Preclinical studies in vitro and in vivo suggested that bortezomib had activity against several hematologic malignancies. Clinical trials of bortezomib in patients with multiple myeloma showed improvements in progression free survival.

FDA approval information for Bortezomib

Bortezomib received approval for use in the United States in 2003 for therapy of multiple myeloma and mantle cell lymphoma when given in combination with other chemotherapeutic agents. Bortezomib is available in powdered form in vials of 3.5 mg under the brand name Velcade.

Dosage and administration for Bortezomib

The typical starting dose is 1.3 mg/m2 intravenously or subcutaneously given once or twice weekly, usually in combination with other agents such as melphalan and prednisone. The recommended dosage and dose regimen varies by indication, tolerance and hepatic function.

Side effects of Bortezomib

• Common side effects include nausea, diarrhea, constipation, anorexia, fatigue, thrombocytopenia, neutropenia, anemia peripheral neuropathy, rash and fever.
• Uncommon, but potentially severe side effects include peripheral neuropathy, cardiac and pulmonary toxicity, bone marrow suppression and tumor lysis syndrome.

Liver safety of Bortezomib

Bortezomib is associated with a low rate of serum enzyme elevations during treatment and to rare instances of clinically apparent, acute liver injury.

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