Oncology
Bortezomib
A boronic-acid dipeptide that blocks the proteasome, and the drug that made multiple myeloma far more treatable.
What it is
Bortezomib (Velcade) is a modified dipeptide carrying a boronic acid group that binds the proteasome reversibly. It was the first proteasome inhibitor approved for cancer and changed the outlook for multiple myeloma. It is a hospital and outpatient cancer medicine given intravenously or under the skin.
How it works
- 1
Binds the chymotrypsin-like active site of the 26S proteasome.
- 2
Blocks degradation of ubiquitin-tagged proteins, including I-kappa-B.
- 3
Stabilised I-kappa-B keeps NF-kappa-B switched off, so survival signals fade.
- 4
Cancer cells accumulate misfolded protein and die, while normal cells tolerate it better.
- 5
Also affects the bone marrow microenvironment that supports myeloma cells.
What it's studied for
Reported and studied effects
- Substantially higher response and survival rates in myeloma than the older melphalan era
- Peripheral neuropathy in a third or more of patients, dose-limiting
- Thrombocytopenia that cycles with the dosing schedule
- Shingles reactivation without antiviral prophylaxis
Research protocol notes
Research context onlyResearch context only - a specialist cancer medicine. The standard schedule is 1.3 mg per square metre on days 1, 4, 8 and 11 of a 21-day cycle, given intravenously or subcutaneously, for up to eight cycles; trials used response rate, progression-free survival and overall survival as endpoints, with antiviral prophylaxis and platelet monitoring throughout.
These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.
Possible side effects and contraindications
Safety profile
Possible side effects
- Peripheral sensory neuropathy, sometimes painful and persistent
- Thrombocytopenia and anaemia
- Herpes zoster reactivation
- Nausea, diarrhoea and constipation
- Fatigue
- Hypotension
- Rare pulmonary toxicity and heart failure
Contraindications and cautions
- Prior hypersensitivity to bortezomib or boron
- Acute diffuse infiltrative pulmonary disease
- Pericardial disease
- Severe neuropathy requires dose modification
- Pregnancy - harmful to the fetus
A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.
Evidence assessment
Multiple large randomised controlled trials in myeloma (APEX, VISTA, and combination studies) with survival endpoints, and worldwide regulatory approval.
References
- 01Richardson et al., A phase 2 study of bortezomib in relapsed, refractory myeloma (APEX), NEJM 2003
- 02European Medicines Agency - Velcade product information
References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.
Related
Related peptides
Other entries in Oncology.