Overview
Bortezomib is a proteasome inhibitor antineoplastic agent used primarily in the treatment of multiple myeloma and mantle cell lymphoma. It reversibly inhibits the 26S proteasome, leading to accumulation of polyubiquitinated proteins, cell cycle arrest, and apoptosis in malignant cells.
Mechanism of Action
Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. Inhibition of the proteasome prevents targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. In vitro, bortezomib causes decreased proliferation and apoptosis in cancer cell lines.
Indications
- Treatment of multiple myeloma
- Treatment of mantle cell lymphoma in patients who have received at least one prior therapy
Dosage
Multiple Myeloma: 1.3 mg/m² administered as an intravenous bolus or subcutaneous injection twice weekly for 2 weeks (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12-21). Mantle Cell Lymphoma: Same dosing schedule. Dose adjustments are required for hematologic and non-hematologic toxicities.
Contraindications
- Hypersensitivity to bortezomib, boron, or mannitol
Side Effects
- Fatigue
- Nausea
- Diarrhea
- Constipation
- Peripheral neuropathy
- Pyrexia
- Vomiting
- Anemia
- Thrombocytopenia
- Neutropenia
- Anorexia
- Asthenia
- Headache
- Insomnia
- Rash
- Edema
- Dyspnea
- Cough
Interactions
- Strong CYP3A4 inhibitors (may increase bortezomib exposure)
- Strong CYP3A4 inducers (may decrease bortezomib exposure)