Bortezomib (Velcade)

==General information==
Class/mechanism: Reversible inhibitor of the 26S proteasome, interfering with degradation of ubiquitinated proteins. This disrupts normal homeostatic mechansims, leading to cell death.Bortezomib (Velcade) package insert Bortezomib (Velcade) package insert (locally hosted backup)Velcade manufacturer's website 
Route: IV, SC
Extravasation: irritant
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, UpToDate Lexidrug, Medscape, or the prescribing information.
==Diseases for which it is established (work in progress)==
*Light-chain (AL) amyloidosis (PMDA)
*Mantle cell lymphoma (EMA, FDA, PMDA)
*Multiple myeloma (EMA, FDA, PMDA)
*Waldenström macroglobulinemia (PMDA)
==Diseases for which it is used==
*B-cell lymphoma of mucosa-associated lymphoid tissue
*Castleman disease
*Follicular lymphoma
*Indolent lymphoma
*Peripheral T-cell lymphoma
*Plasma cell leukemia
==Diseases for which it was used==
*Diffuse large B-cell lymphoma
==Notable side effects==
*HSV reactivation Chanan-Khan A, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Neuwirth R, Anderson KC, Richardson PG. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol. 2008 Oct 10;26(29):4784-90. Epub 2008 Aug 18. link to original article EuroPMCVickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009 Jan 1;115(1):229-32. link to original article EuroPMC
**Use antiviral prophylaxis (such as with acyclovir (Zovirax) 400 mg PO once per day or valacyclovir (Valtrex) 250 to 500 mg PO once per day) to decrease risk of reactivating herpes zoster in patients treated with bortezomib
*Neuropathy Broyl A, Corthals SL, Jongen JL, van der Holt B, Kuiper R, de Knegt Y, van Duin M, el Jarari L, Bertsch U, Lokhorst HM, Durie BG, Goldschmidt H, Sonneveld P. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol. 2010 Nov;11(11):1057-65. Epub 2010 Sep 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Patient drug information==
*Bortezomib (Velcade) patient drug information (Chemocare)Bortezomib (Velcade) patient drug information (Chemocare)
*Patient counseling information can be found in the package insert
*Bortezomib (Velcade) patient drug information (UpToDate)Bortezomib (Velcade) patient drug information (UpToDate)
==History of changes in FDA indication==
===Mantle cell lymphoma===
*2006-12-08: Approved for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. (New disease entity; based on PINNACLE)
*2014-10-08: Approved for treatment of patients with mantle cell lymphoma. (including first-line therapy for untreated patients; previously was only approved for patients who had received at least one prior treatment; based on LYM-3002)
===Multiple myeloma===
*2003-05-13: Initial accelerated approval for the treatment of multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. (Based on SUMMIT)
*2005-03-25: Converted to regular approval for the treatment of multiple myeloma patients who have received at least 1 prior therapy. (Based on APEX)
*2008-06-23: Approved for the treatment of patients with multiple myeloma. (previously was only approved for patients who had received prior therapy; based on VISTA)
*2012-01-23: Approved for subcutaneous administration of patients with multiple myeloma. (Based on MMY-3021)
*2014-08-11: Approved for retreatment of patients with multiple myeloma. (Based on RETRIEVE)
==History of changes in EMA indication==
*2004-04-26: Initial marketing authorization as Velcade.
*2013-07-31: Velcade in combination with dexamethasone is indicated for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
*2013-07-31: Velcade in combination with dexamethasone and thalidomide is indicated for the induction treatment of adult patients with previously untreated multiple myeloma who are eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
*2013-12-18: Extension of indication for Velcade in combination with pegylated liposomal doxorubicin in patients with relapsed and /or progressive multiple myeloma who have received at least 1 prior therapy.
*2013-12-18: Extension of indication for Velcade in combination with dexamethasone in patients with relapsed and /or progressive multiple myeloma who have received at least 1 prior therapy.
*2015-01-30: Extension of indication for the use of VELCADE in combination with rituximab, cyclophosphamide, doxorubicin and prednisone for the treatment of adult patients with previously untreated mantle cell lymphoma.
*Uncertain date: Velcade as monotherapy is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
*Uncertain date: Velcade in combination with pegylated liposomal doxorubicin is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
*Uncertain date: Velcade in combination with dexamethasone is indicated for the treatment of adult patients with progressive multiple myeloma who have received at least 1 prior therapy and who have already undergone or are unsuitable for haematopoietic stem cell transplantation.
*Uncertain date: Velcade in combination with melphalan and prednisone is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for high dose chemotherapy with haematopoietic stem cell transplantation.
*Uncertain date: Velcade in combination with rituximab, cyclophosphamide, doxorubicin and prednisone is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma who are unsuitable for haematopoietic stem cell transplantation.
==History of changes in Health Canada indication==
*2005-01-27: Initial notice of compliance with conditions
*2007-09-11: Conditions were met
==History of changes in PMDA indication==
*2006-10-20: Initial approval for treatment of relapsed or refractory multiple myeloma.
*2011-09-16: New indication and a new dosage for the treatment of multiple myeloma.
*2012-12-21: New route of administration indicated for the treatment of multiple myeloma.
*2015-06-26: New additional indication and a new dosage for the treatment of patients with mantle cell lymphoma.
*2018-03-23: New additional indication and a new dosage indicated for the treatment of Waldenström's macroglobulinemia and lymphoplasmacytic lymphoma.
*2021-08-25: New indication and a new dosage for the treatment of systemic AL amyloidosis.
==Also known as==
*Code names: LDP-341, MLN-341, PS-341
*Brand names: Biocure, Bortecad, Bortecine, Borteget, Bortemib, Bortenat, Bortetrust, Bortier, Bortesal, Bortesam, Bortlee, Bortlieva, Bortmap, Bortiac, Bortezest, Borater, Bortrac, Borvex, Borviz, Botepar, Bromadene, Chemobort, Egybort, M-prib, Mezomib, Mibor, Myezom, Norvelzo, Ortez, Tezomin, Velcade, Veltip, Zomib, Zuricade
==References==
Category:Drugs
Category:Intravenous medications
Category:Subcutaneous medications
Category:Irritant
Category:Proteasome inhibitors
Category:Castleman disease medications
Category:Follicular lymphoma medications
Category:Indolent lymphoma medications
Category:Light-chain (AL) amyloidosis medications
Category:MALT lymphoma medications
Category:Mantle cell lymphoma medications
Category:Multiple myeloma medications
Category:Peripheral T-cell lymphoma medications
Category:Plasma cell leukemia medications
Category:Waldenström macroglobulinemia medications
Category:Diffuse large B-cell lymphoma medications (historic)
Category:EMA approved in 2004
Category:FDA approved in 2003
Category:Health Canada approved in 2005
Category:PMDA approved in 2006
Category:WHO Essential Cancer Medicine