bortezomib

Bortezomib is a small-molecule proteasome inhibitor used in the treatment of cancer. Marketed as Velcade, it was the first clinically approved proteasome inhibitor and is manufactured by Janssen. It is primarily used for multiple myeloma and mantle cell lymphoma and is employed in several combination regimens.

Bortezomib reversibly inhibits the 26S proteasome, with activity against the chymotrypsin-like β5 subunit. Inhibition leads to the accumulation of ubiquitinated proteins, disruption of signaling pathways including NF-κB, and induction of apoptosis in malignant cells, particularly plasma cells in multiple myeloma.

Administration typically involves 1.3 mg/m2 given by intravenous or subcutaneous injection on days 1, 4, 8, and 11 of a 21-day cycle. Subcutaneous administration reduces the risk and severity of cumulative peripheral neuropathy compared with intravenous dosing; both routes are effective and commonly used in practice.

Adverse effects commonly include peripheral neuropathy, fatigue, thrombocytopenia, nausea, diarrhea, and risk of infections such as herpes zoster. Additional risks include cytopenias, hypophosphatemia, and infusion-related reactions. Dosing may be adjusted for neuropathy or cytopenias, and patients are monitored for hematologic and neurologic toxicity.

Development and approvals: Bortezomib was developed by Millennium Pharmaceuticals and later marketed by Janssen. It received FDA approval in 2003 for multiple myeloma after prior therapy and has since gained additional indications, including mantle cell lymphoma. A subcutaneous formulation, approved to reduce neuropathy risk, is widely used in clinical practice.