Bortezomib (Velcade) is a targeted therapeutic agent indicated for the treatment of multiple myeloma and mantle cell lymphoma, belonging to the class of proteasome inhibitors.
Mechanism of Action of Bortezomib
1. Proteasome Inhibition
(1) Bortezomib is a reversible proteasome inhibitor that primarily targets the chymotrypsin-like activity of the 26S proteasome.
(2) The proteasome is responsible for the degradation of ubiquitinated proteins within cells, maintaining intracellular homeostasis.
(3) Inhibition of proteasome function leads to the accumulation of abnormal proteins, disruption of cellular signaling pathways, and ultimately induction of cancer cell apoptosis.
2. Antitumor Effects
(1) Preclinical studies have demonstrated that bortezomib exhibits cytotoxicity against various cancer cell lines and can delay tumor growth in animal models.
(2) Its antitumor activity is not limited to direct induction of apoptosis; it may also modulate the tumor microenvironment and inhibit angiogenesis.
Drug Interactions
1. Strong CYP3A4 Inducers
Concomitant use of strong CYP3A4 inducers (e.g., rifampicin) significantly reduces plasma concentrations of bortezomib, which may impair its efficacy. Co-administration should be avoided.
2. Strong CYP3A4 Inhibitors
(1) Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole) increases bortezomib exposure and raises the risk of toxicity.
(2) If co-administration is necessary, patients should be closely monitored for signs of toxicity, and dose reduction of bortezomib should be considered.
3. Drugs Without Significant Interactions
No clinically significant drug interactions have been observed when bortezomib is co-administered with dexamethasone, omeprazole, or melphalan plus prednisone.
Clinical Precautions
1. Dosage and Administration Route
(1) Bortezomib may be administered via intravenous injection or subcutaneous injection; intrathecal administration is contraindicated.
(2) Reconstitution concentrations differ between administration routes, so careful calculation of the injection volume is required.
(3) The recommended starting dose is 1.3 mg/m². A reduced starting dose is required for patients with moderate to severe hepatic impairment.
2. Common Adverse Reactions and Management
(1) The most frequent adverse reactions include nausea, diarrhea, thrombocytopenia, and peripheral neuropathy.
(2) Dosing should be interrupted for non-hematological toxicity ≥ Grade 3 or hematological toxicity Grade 4. Treatment may be resumed at a reduced dose after recovery.
(3) For patients with peripheral neuropathy, switching to subcutaneous administration and dose adjustment or treatment interruption based on severity may be considered.
3. Use in Special Populations
(1) Dose adjustment is required for patients with hepatic impairment based on bilirubin and transaminase levels.
(2) Blood glucose should be closely monitored in diabetic patients, and antidiabetic medications adjusted accordingly during treatment.
(3) Bortezomib is contraindicated in pregnant women. Effective contraception must be used during treatment and after therapy in patients of reproductive potential.
(4) Lactating women should discontinue breastfeeding during treatment and for two months after the last dose.
4. Important Warnings and Risks
(1) The following serious risks should be monitored during treatment:
peripheral neuropathy, hypotension, heart failure, pulmonary toxicity, posterior reversible encephalopathy syndrome, thrombocytopenia/neutropenia, tumor lysis syndrome, hepatotoxicity, and thrombotic microangiopathy.
(2) Medical attention should be sought promptly if relevant symptoms occur, and treatment adjustment should be considered.
