Bortezomib

Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma.[3] This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection.[3]

Common side effects include nausea, diarrhea, tiredness, low platelets, fever, numbness, low white blood cells, shortness of breath, rash and abdominal pain.[3] Other severe side effects include low blood pressure, tumour lysis syndrome, heart failure, and reversible posterior leukoencephalopathy syndrome.[3] It is in the class of medications known as proteasome inhibitor.[3] It works by inhibiting proteasomes, cellular complexes that break down proteins.

Bortezomib was approved for medical use in the United States in 2003 and in the European Union in 2004.[3][4] It is on the World Health Organization's List of Essential Medicines.[5] It is available as a generic medication.[6]

Medical use

Two open-label trials established the efficacy of bortezomib (with or without dexamethasone) on days 1,4,8, and 11 of a 21-day cycle for a maximum of eight cycles in heavily pretreated people with relapsed/refractory multiple myeloma.[7] The phase III demonstrated the superiority of bortezomib over a high-dose dexamethasone regimen (e.g. median TTP 6.2 vs 3.5 months, and 1-year survival 80% vs 66%).[7] New studies show that bortezomib may potentially help recover from vincristine treatment in treating acute lymphoblastic leukemia, when replacing vincristine in the process.[8]

Bortezomib was also evaluated together with other drugs for the treatment of multiple myelomas in adults. It was seen that bortezomib plus lenalidomide plus dexamethasone as well as bortezomib plus melphalan and prednisone may result in a large increase in the progression-free survival.[9]

Adverse effects

Gastro-intestinal effects and asthenia are the most common adverse events.[10] Bortezomib is associated with peripheral neuropathy in 30% of people resulting in pain. This can be worse in people with pre-existing neuropathy. In addition, myelosuppression causing neutropenia and thrombocytopenia can also occur and be dose-limiting. However, these side effects are usually mild relative to bone marrow transplantation and other treatment options for people with advanced disease. Bortezomib is associated with a high rate of shingles,[11] although prophylactic acyclovir can reduce the risk of this.[12]

Ocular side effects such as chalazion or hordeolum (stye) may be more common in women and have led to discontinuation of treatment.[13]

Drug interactions

Polyphenols derived from green tea extract including epigallocatechin gallate (EGCG), which were expected to have a synergistic effect, instead were found to reduce the effectiveness of bortezomib in cell culture experiments.[15]

Pharmacology

History

Bortezomib was originally made in 1995 at Myogenics. The drug (PS-341) was tested in a small Phase I clinical trial on people with multiple myeloma. It was brought to further clinical trials by Millennium Pharmaceuticals in October 1999.[21]

In May 2003, bortezomib (marketed as Velcade by Millennium Pharmaceuticals Inc.) was approved in the United States by the Food and Drug Administration (FDA) for use in multiple myeloma, based on the results from the SUMMIT Phase II trial.[22][23] In 2008, bortezomib was approved in the United States for initial treatment of people with multiple myeloma.[24] Bortezomib was previously approved in 2005, for the treatment of people with multiple myeloma who had received at least one prior therapy and in 2003, for the treatment of more refractory multiple myeloma.[24]

Society and culture

External links