Summary of bevacizumab side effects:
1.bevacizumab side effects: Hypertension:
Mechanism: During the anti-tumor process of bevacizumab, VEGF is blocked, leading to a decrease in nitric oxide levels, which causes blood vessels to be unable to dilate, increasing peripheral resistance and causing hypertension. Additionally, lower levels of nitric oxide are also associated with reduced renal excretion, leading to water and sodium retention and further elevating blood pressure. Hypertension related to bevacizumab is controllable and treatable, with a ≥ grade 3 hypertension incidence rate of 5% to 9%.
Management Principles:
Monitor baseline blood pressure before starting the medication. If there is a history of hypertension, or if the patient’s blood pressure is significantly higher than the baseline, it is recommended to start antihypertensive medication with a target blood pressure of 140 mmHg/90mmHg (1mmHg=0.133 kPa). For high-risk patients, blood pressure should be controlled at 130mmHg/80mmHg.
During medication use, enhance blood pressure monitoring. Antihypertensive drugs can include: angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARB), β-blockers, and calcium channel blockers.
If a patient experiences moderate or higher hypertension (blood pressure above 160mmHg/100mmHg) and antihypertensive drugs temporarily cannot control it, bevacizumab should be paused and antihypertensive treatment given until blood pressure is controlled. If hypertension is not controlled after 1 month of treatment or if hypertensive crisis or hypertensive encephalopathy occurs, bevacizumab should be discontinued.
2.bevacizumab side effects: Bleeding:
Mechanism: Blocking VEGF deactivates it, reducing nitric oxide levels, affecting platelet activation; simultaneously, inhibiting the VEGF pathway affects endothelial cell survival and proliferation, leading to compromised vascular integrity, especially in tissues with high VEGF dependency, such as damage to the airway mucosa. The incidence rate of ≥ grade 3 hemoptysis is 1.0% to 4.4%.
Management Principles:
Screen for high-risk bleeding populations before medication:
- Patients with cavitated or centrally located squamous cell NSCLC;
- Patients treated with long-term or high-dose anti-rheumatic/anti-inflammatory drugs or anticoagulation therapy;
- Patients with large primary lesions that have undergone radiation therapy;
- Patients with a history of arteriosclerosis;
- Patients with peptic ulcers, etc.;
- Patients with recent signs of bleeding in the tumor, should be cautious when using anti-angiogenesis drugs;
- Patients who have had pulmonary hemorrhage, hemoptysis (>3ml of fresh blood) within the last 3 months are prohibited from use.
During medication, if a grade 1 bleeding event occurs, there is no need to adjust the dose of anti-angiogenesis drugs. For minor nosebleeds and blood in sputum, no treatment is necessary, or nasal or oral administration of Panax notoginseng powder, Yunnan Baiyao, etc., can be considered. If a grade 2 bleeding event occurs, pause treatment and consider continuing anti-vascular drugs after active hemostasis. If a ≥ grade 3 bleeding event occurs, permanent discontinuation is required.
3.bevacizumab side effects: Proteinuria:
Mechanism: Inhibiting the VEGF pathway can lead to loss of fenestrations, endothelial edema, and detachment in glomerular capillaries, thereby damaging the integrity of the filtration barrier, resulting in proteinuria. The incidence rate of ≥ grade 3 proteinuria is <1% to 4%.
Management Principles:
- Protein testing should be conducted before medication use, 24 h urine protein quantification: If urine protein levels are ≥ 2 g/24 h, delay anti-angiogenesis drug treatment until urine protein levels return to <2 g/24 h.
- Adjust the use of drugs according to the condition of urine protein after the occurrence of proteinuria during the medication process: For urine protein 1+ to 3+ or 24 h urine protein <2 g, continue to give anti-angiogenesis drugs according to the predetermined plan; For urine protein 4+ or 24 h urine protein ≥ 2 g, pause the current medication plan, delay administration until 24 h urine protein <2 g; For grade 4 proteinuria (nephrotic syndrome), permanently stop the medication.
- For proteinuria, first-line treatment can include ACEI or ARB, second-line treatment includes non-dihydropyridine calcium channel blockers or aldosterone receptor antagonists. Consult a specialist if necessary.
- After discontinuing bevacizumab treatment, patients should have their 24 h urine protein checked every 3 months until 24 h urine protein <1 g.
4.bevacizumab side effects: Thromboembolic Events:
Mechanism: Blocking VEGF can affect the repair process of damaged endothelial surfaces, leading to exposure of endothelial tissue and apoptosis of endothelial cells, while stimulating prothrombin factor III, thereby triggering the coagulation cascade and forming blood clots. Endothelial cell apoptosis may lead to downregulation of anticoagulant factors thrombomodulin and heparan sulfate, and redistribution of phosphatidylserine, which can enhance the procoagulant activity of prothrombin factor X. The incidence rate of ≥ grade 3 thromboembolic events is 0 to 7%.
Management Principles:
- Identify high-risk thrombosis groups before medication: Patients with a history of arterial or venous thromboembolism; diabetes or age >65 years, as well as patients prone to vascular disease (such as a history of cardiac stent placement); patients receiving combined anti-angiogenesis drug and chemotherapy treatment.
- Adopt different strategies for different types of thrombosis during the medication process:
- (1) Arterial thromboembolic events (ATE): Once any level of thrombosis occurs, bevacizumab treatment should be suspended during the acute phase; patients who have recently experienced ATE cannot use bevacizumab treatment for at least 6 months after the ATE occurrence, and it should be confirmed that the patient is in a stable condition or asymptomatic before starting bevacizumab treatment. Consult a specialist if necessary.
- (2) Venous thromboembolic events (VTE): For patients experiencing ≤ grade 3 VTE, drug treatment can be resumed after starting low molecular weight heparin anticoagulation treatment; for patients with grade 4 venous thromboembolism or recurrent or refractory thromboembolism after anticoagulation treatment, medication should be terminated.
Bevacizumab, marketed under the brand name Avastin, is a biopharmaceutical drug designed to interfere with the growth and spread of cancer cells. As a monoclonal antibody, it specifically targets the vascular endothelial growth factor (VEGF), a protein that stimulates the formation of new blood vessels (angiogenesis) necessary for tumor growth. This article delves into the aspects of bevacizumab, including its uses, side effects, indications, contraindications, precautions, dosage, development history, manufacturers in the United States, and its pricing.
Introduction
Developed by Genentech, a subsidiary of Roche, bevacizumab was the first clinically available angiogenesis inhibitor in the United States. Its approval by the FDA in February 2004 marked a significant milestone in cancer therapy, offering a new avenue for treatment. Bevacizumab is used in combination with other chemotherapy drugs to treat various cancers, including colorectal, lung, glioblastoma, kidney, and ovarian cancers.
Side Effects and Adverse Reactions
While bevacizumab has proven beneficial in treating several types of cancer, it comes with a range of side effects. Common adverse reactions include hypertension, fatigue, diarrhea, and decreased white blood cell counts, which can increase the risk of infection. More serious side effects involve gastrointestinal perforations, severe bleeding, thromboembolism, and impaired wound healing. Due to its mechanism of inhibiting blood vessel formation, bevacizumab can also lead to delayed wound healing and increased risk of bleeding.
Indications
Bevacizumab is indicated for the treatment of various cancers, including metastatic colorectal cancer, non-squamous non-small cell lung cancer (NSCLC), recurrent glioblastoma, metastatic renal cell carcinoma, and persistent, recurrent, or metastatic cervical cancer. Its use is generally reserved for cases where other treatments have failed or as part of a combination therapy to increase efficacy.
Contraindications and Precautions
Bevacizumab is contraindicated in patients with hypersensitivity to bevacizumab or any of its components, and in patients with severe hemorrhage, thromboembolism, or gastrointestinal perforation. Caution is advised when using bevacizumab in patients with a history of arterial thromboembolic events, recent surgery, or in those with pre-existing hypertension.
Dosage and Administration
The dosage of bevacizumab varies depending on the type of cancer being treated. It is typically administered as an intravenous infusion. For example, in the treatment of metastatic colorectal cancer, the recommended dose is 5 mg/kg of body weight given once every 2 weeks as part of combination chemotherapy. The dosing schedule may vary for other types of cancer, and adjustments may be necessary based on patient response and tolerability.
Development History
The discovery of bevacizumab can be traced back to the early 1990s, when researchers began to understand the role of angiogenesis in tumor growth. The development of bevacizumab was based on the premise that blocking angiogenesis could starve tumors of the necessary blood supply to grow and spread. After years of research and clinical trials, bevacizumab became the first anti-angiogenic drug to receive FDA approval for cancer treatment.
Manufacturers in the United States and Pricing
In the United States, bevacizumab is produced by Genentech, a leading biotechnology company. The cost of bevacizumab can be quite high, often exceeding several thousand dollars per dose. The price depends on the treatment regimen, dosage, and duration of therapy. Despite its high cost, bevacizumab has been a valuable addition to cancer therapy, offering hope to patients with advanced cancers.
Conclusion
Bevacizumab represents a significant advancement in the treatment of cancer, providing a targeted approach to inhibiting tumor growth. While its side effects can be challenging to manage, the benefits it offers in terms of improved survival and quality of life for cancer patients are undeniable. As research continues, further therapeutic applications and improvements in the administration of bevacizumab may emerge, continuing to make it a cornerstone of cancer therapy.