Bevacizumab – Uses, Dosage, Side Effects, Interactions

Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A (VEGF-A). It is used to treat several different cancers (cervical? cancer, metastatic colorectal cancer, glioblastoma, non-squamous non-small cell lung cancer, ovarian, fallopian tube?, primary peritoneal cancer, metastatic renal? cell carcinoma?, and hepatocellular carcinoma ). The administration of bevacizumab inhibits microvascular growth and angiogenesis and is used in cancer treatment to inhibit malignant? cell growth and blood vessel formation. It is usually administered in combination with other chemotherapy? agents. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring?, relevant interactions) pertinent for members of the interprofessional team in the treatment of patients with bevacizumab.

Mechanism of Action

Bevacizumab is a recombinant humanized monoclonal antibody that binds to all known vascular endothelial growth factor A (VEGF-A) isoforms. It blocks the interaction between VEGF-A and the VEGF receptors (VEGFR), primarily VEGFR-1 (fit-1) and VEGFR-2 (KDRflk-1), on the surface of endothelial cells. It is 93% human and 7% murine in the protein sequence. The binding of VEGF-A to VEGFR-1 and VEGFR-2 leads to endothelial cell proliferation, the activation of survival pathways, and the formation of new blood vessels and angiogenesis. Therefore, the administration of bevacizumab inhibits microvascular growth and angiogenesis and is used in cancer treatment to inhibit malignant cell growth and blood vessel formation.[rx]

or

Transcription of the VEGF protein is induced by a ‘hypoxia? inducible factor (HIF) in a hypoxic environment.¹⁴ When circulating VEGF binds to VEGF receptors (VEGFR-1 and VEGFR-2) located on endothelial cells, various downstream effects are initiated.^5,14 It should be noted that VEGF also binds to the neuropilin co-receptors (NRP-1 and NRP-1), leading to enhanced signaling.^14,17

Cancer cells promote tumor? angiogenesis by releasing VEGF, resulting in the creation of an immature and disorganized vascular network.^9,10 The hypoxic microenvironment promoted by cancer cells favors the survival of more aggressive tumor cells and gives rise to a challenging environment for immune cells to respond appropriately.^10,11,12 As a result, VEGF has become a well-known target for anti-cancer drugs like bevacizumab.⁶ Bevacizumab is a mAb that exerts its effects by binding and inactivating serum VEGF.¹⁴ When bound to the mAb, VEGF is unable to interact with its cell surface receptors, and proangiogenic signaling is inhibited.¹⁴ This prevents the formation of new blood vessels, decreases tumor vasculature, and reduces tumor blood supply.^14,25

There is also evidence to suggest that VEGF is upregulated in COVID-19 patients, hence, bevacizumab is being investigated for the treatment of associated complications.²⁶ Higher levels of VEGF may contribute to pulmonary edema?, leading to acute respiratory distress syndrome? (ARDS?) and acute? lung injury (ALI).²⁶ Researchers are hopeful that by inhibiting VEGF, bevacizumab may effectively treat ARDS and ALI – both common features of severe? COVID-19 cases.²⁶

Pharmacokinetics

Absorption: A PK study concluded bevacizumab follows linear pharmacokinetics and is expected to reach 90% of steady-state concentration by 84 days.[rx]

Distribution: The volume of distribution is 2.9 L. After correcting for body weight, males have a larger central volume of distribution (3.2 L vs. 2.7 L) than females.[rx]

Metabolism: The metabolism of bevacizumab is likely identical to endogenous antibodies like IgG, i.e., by proteolytic catabolism, involving non-specific elimination pathways and target-mediated elimination by VEGF-expressing cells. Hence it doesn’t affect the activity of drug-metabolizing enzymes in the liver?.[rx][rx]

Elimination: The mean clearance is 0.23 L/day. After correcting for body weight, clearance is approximately 26% higher in men than in women. The estimated half-life is 20 days. The clearance of bevacizumab alters by body weight, sex, and tumor burden. Clearance is reduced with increased albumin and reduced alkaline phosphatase.[rx][rx]

Indications

Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor A (VEGF-A) and is used to treat the below conditions. Its use is typically in combination with other chemotherapy agents.[rx][rx][rx]

FDA-approved Indications

1. Cervical cancer: Bevacizumab has approval for treating recurrent?, persistent, or metastatic cervical cancer in combination with paclitaxel and either cisplatin or topotecan.
2. Metastatic colorectal cancer: Bevacizumab is a first-line or second-line therapy for metastatic colorectal cancer combined with fluorouracil (FU)-based chemotherapy regimens.
3. Glioblastoma: Bevacizumab has approval as a single agent in patients with progressive glioblastoma following previous therapy.
4. Non-squamous non-small cell lung cancer (NSCLC): Bevacizumab is a first-line treatment combination with carboplatin and paclitaxel for recurrent, locally advanced, unresectable, or metastatic non-squamous non-small cell lung cancer.[rx]
5. Ovarian, fallopian tube, or primary peritoneal cancer: Bevacizumab has approved the treatment of platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with a carboplatin chemotherapy regimen or the treatment of platinum-resistant disease in combination with paclitaxel, doxorubicin, or topotecan.[rx]
6. Metastatic renal cell carcinoma: Bevacizumab has received approval to treat metastatic renal cell carcinoma in combination with interferon alfa.
7. Hepatocellular carcinoma (HCC): Bevacizumab, in combination with atezolizumab, is indicated for treating unresectable metastatic hepatocellular carcinoma patients.[rx]
8. As a vascular endothelial growth factor (VEGF) inhibitor, bevacizumab is used in several chemotherapy regimens to treat metastatic colorectal cancer; metastatic, unresectable, locally advanced or recurrent non-squamous non-small cell lung cancer; metastatic renal cell carcinoma; metastatic, persistent, or recurrent cervical cancer; primary peritoneal cancer; epithelial ovarian cancer; fallopian tube cancer; breast cancer; and recurrent glioblastoma.²⁵Interestingly, bevacizumab is currently under investigation for the treatment of COVID-19 complications including acute respiratory distress syndrome? (ARDS) and acute lung injury (ALI).²⁶

Off-label Indications

1. Metastatic breast cancer[rx]
2. Endometrial cancer
3. Angiosarcoma
4. Gliomas
5. Malignant pleural mesothelioma
6. Medulloblastoma (pediatric)
7. Diabetic macular edema
8. Age-related macular degeneration
9. Hemangiopericytoma and malignant solitary fibrous tumor
10. Hereditary? hemorrhagic telangiectasia[rx]

Associated Conditions

• Metastatic Breast Cancer
• Metastatic Cervical Cancer
• Metastatic Colorectal Cancer (CRC)
• Metastatic Non-squamous Non-Small Cell Lung Cancer
• Metastatic Renal Cell Carcinoma ( mRCC)
• Persistent Cervical Cancer
• Recurrent Cervical Cancer
• Recurrent Glioblastoma
• Stage III Fallopian Tube Cancer
• Stage III Primary Peritoneal Cancer
• Stage IV Fallopian Tube Cancer
• Stage IV Ovarian Epithelial Cancer
• Stage IV Primary Peritoneal Cancer
• Locally advanced nonsquamous non-small cell lung cancer
• Recurrent Non-Squamous Non-Small Cell Lung Cancer
• Recurrent Platinum-Sensitive Epithelial Ovarian Cancer
• Recurrent Platinum-resistant Epithelial Ovarian Cancer
• Recurrent platinum drug-resistant Fallopian tube cancer
• Recurrent platinum drug-resistant primary peritoneal cancer
• Recurrent platinum-sensitive primary peritoneal cancer
• Recurrent platinum-sensitive fallopian tube cancer
• Stage 3 Ovarian Epithelial Cancer
• Unresectable Non-Squamous Non-Small Cell Lung Cancer
• Unresectable, advanced Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

Use in Cancer

Bevacizumab is approved to be used alone or with other drugs to treat:

• Cervical cancer that has not gotten better with other treatments, has spread to other parts of the body or has come back. It is used with paclitaxel and either cisplatin or topotecan hydrochloride. This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.
• Colorectal cancer has spread to other parts of the body. It is used:
  • With fluorouracil as the first or second treatment.
  • Fluoropyrimidine and either irinotecan hydrochloride or oxaliplatin as the second treatment in patients whose disease has gotten worse after therapy that included bevacizumab.

  This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.

• Glioblastoma (a type of brain cancer) has come back. It is used in adults. This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.
• Hepatocellular carcinoma (a type of liver cancer) has spread to other parts of the body or cannot be removed by surgery. It is used with atezolizumab in patients who have not received systemic? therapy. This use is approved for the Avastin brand of bevacizumab.
• Nonsquamous non-small cell lung cancer that has spread, cannot be removed by surgery, or has come back. It is used with carboplatin and paclitaxel as the first therapy. This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.
• Ovarian epithelial, fallopian tube, or primary peritoneal cancer. It is used:
  • With carboplatin and paclitaxel and then alone in patients with stage III, stage IV, or recurrent cancer. It is given after surgery. This use is approved for the Avastin, Mvasi, and Zirabev brands of bevacizumab.
  • Paclitaxel, doxorubicin hydrochloride liposome, or topotecan hydrochloride in patients whose cancer has come back, does not respond to platinum chemotherapy and has been treated with up to two types of chemotherapy. This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.
  • With carboplatin and paclitaxel or carboplatin and gemcitabine hydrochloride and then alone in patients whose cancer responds to platinum chemotherapy and has come back. This use is approved for the Avastin, Mvasi, and Zirabev brands of bevacizumab.
• Renal cell carcinoma (a type of kidney? cancer) has spread to other parts of the body. It is used with interferon-alpha. This use is approved for the Alymsys, Avastin, Mvasi, and Zirabev brands of bevacizumab.

Bevacizumab is also being studied in the treatment of other types of cancer.

Contraindications

There are currently no contraindications listed for bevacizumab. Bevacizumab should not be administered in a dextrose solution due to the formation of insoluble aggregates.[rx]

The following conditions are contraindicated? with this drug. Check with your physician if you have any of the following:

• low levels of female hormones in the body called hypogonadism
• decrease of neutrophils in the blood from cancer chemotherapy
• low levels of a type of white blood cell called neutrophils
• high blood pressure
• a heart attack?
• angina?, a type of chest pain?
• chronic? heart failure?
• a hemorrhage in the brain
• a transient ischemic attack?, a type of stroke? that lasts only a few minutes
• obstruction of a blood vessel by a blood clot
• inflammation of the esophagus with erosion
• an abnormal connection between the esophagus and windpipe
• a gastrointestinal tract fistula
• bleeding of the stomach or intestines
• nephrotic syndrome, a type of kidney disorder
• bleeding not related to the menstrual period
• recent operation
• elevation of proteins in the urine
• impaired wound healing
• pregnancy
• a patient who is producing milk and breastfeeding
• a rupture in the wall of the stomach or intestine
• problems with wound healing after a surgery
• a type of brain disorder called posterior reversible encephalopathy syndrome
• a fistula between two body organs
• secondary ovarian failure, a condition where ovaries stop working before age 40
• necrotizing fasciitis
• bleeding in the alveoli of the lungs

Dosage

Strengths: over 25 mg/mL; 25 mg/mL; aww 25 mg/mL; maly 25 mg/mL

Usual Adult Dose

Colorectal Cancer

• In combination with bolus-IFL: 5 mg/kg IV every 2 weeks
• In combination with FOLFOX4: 10 mg/kg IV every 2 wee
• In combination with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin-based chemotherapy regimen in patients who have progressed on a first-line bevacizumab-containing regimen: 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks
• Duration of therapy: Until disease progression or unacceptable toxicity

Non-Small Cell Lung Cancer

• In combination with carboplatin and paclitaxel: 15 mg/kg IV every 3 weeks
• Duration of therapy: Until disease progression or unacceptable toxicity
  

Glioblastoma Multiforme

• 10 mg/kg IV every 2 weeks
• Duration of therapy: Until disease progression or unacceptable toxicity

Renal Cell Carcinoma

• In combination with interferon alfa: 10 mg/kg IV every 2 weeks
• Duration of therapy: Until disease progression or unacceptable toxicity

Cervical Cancer

• In combination with paclitaxel and cisplatin OR paclitaxel and topotecan: 15 mg/kg IV every 3 weeks
• Administer the first infusion over 90 minutes, the second over 60 minutes if the first infusion is tolerated, and all subsequent infusions over 30 minutes if the infusion over 60 minutes is tolerated.

Ovarian Cancer

TREATMENT OF STAGE III OR IV DISEASE FOLLOWING INITIAL SURGICAL RESECTION:

• 15 mg/kg IV every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent, for a total of up to 22 cycles or until disease progression, whichever occurs earlier

TREATMENT OF RECURRENT DISEASE:
PLATINUM RESISTANT:

• 10 mg/kg IV every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week)
• Give 15 mg/kg IV every 3 weeks in combination with topotecan (every 3 weeks)

PLATINUM SENSITIVE:

• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent until disease progression
• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression
• In combination with carboplatin and paclitaxel, followed by bevacizumab as a single agent, for the treatment of patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection
• In combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, for the treatment of patients with a platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens
• In combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by bevacizumab as a single agent, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer

Fallopian Tube Cancer

TREATMENT OF STAGE III OR IV DISEASE FOLLOWING INITIAL SURGICAL RESECTION:

• 15 mg/kg IV every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent, for a total of up to 22 cycles or until disease progression, whichever occurs earlier

TREATMENT OF RECURRENT DISEASE:
PLATINUM RESISTANT:

• 10 mg/kg IV every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week)
• Give 15 mg/kg IV every 3 weeks in combination with topotecan (every 3 weeks)

PLATINUM SENSITIVE:

• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent until disease progression
• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression

Peritoneal Cancer

TREATMENT OF STAGE III OR IV DISEASE FOLLOWING INITIAL SURGICAL RESECTION:

• 15 mg/kg IV every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent, for a total of up to 22 cycles or until disease progression, whichever occurs earlier

TREATMENT OF RECURRENT DISEASE:
PLATINUM RESISTANT:

• 10 mg/kg IV every 2 weeks in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan (every week)
• Give 15 mg/kg IV every 3 weeks in combination with topotecan (every 3 weeks)

PLATINUM SENSITIVE:

• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and paclitaxel for 6 to 8 cycles, followed by bevacizumab 15 mg/kg IV every 3 weeks as a single agent until disease progression
• Give 15 mg/kg IV every 3 weeks, in combination with carboplatin and gemcitabine for 6 to 10 cycles, followed by bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression

Hepatocellular Carcinoma

• 15 mg/kg IV (after administration of atezolizumab 1200 mg IV on the same day) every 3 weeks until disease progression or unacceptable toxicity
  Bevacizumab administration is via intravenous (IV) infusion. Bevacizumab comes in 100 mg and 400 mg solutions in 4 mL and 16 mL, respectively.[rx] The first infusion should be over 90 minutes and subsequent infusions over 60 minutes if the first infusion is well tolerated. Additional infusions can be given over 30 minutes if the patient takes the 60-minute infusion well.
• There are many different dosing regimens based on the type of cancer treated; most fall between 5 mg to 15 mg/kg body weight on a cyclical treatment schedule (14 or 21 days), also depending on the type of cancer being treated.[rx] Bevacizumab is also given off-label as an intravitreal injection for ophthalmic conditions such as macular edema and age-related macular degeneration.[rx]

Side Effects

Cardiovascular

• Hypertension (19% to 42%), venous thromboembolism (secondary: 21%; with oral anticoagulants), peripheral edema (15%), hypotension (7% to 15%)

Central Nervous System

• Fatigue (33% to 82%), pain (8% to 62%), headache (22% to 49%), dizziness (13% to 26%), insomnia (21%), taste disorder (14% to 21%), peripheral sensory neuropathy (17% to 18%), anxiety (17%), myasthenia (13%)

Dermatology

• Alopecia (6% to 32%), exfoliative dermatitis (23%), palmar-plantar erythrodysesthesia (11%)

Endocrine

• Hyperglycemia (26% to 31%), hypomagnesemia (24% to 27%), weight loss (15% to 21%), hyponatremia (17% to 19%), hypoalbuminemia (11% to 16%), hypocalcemia (12%)

Gastrointestinal

• Nausea (72%), abdominal pain (33% to 61%), vomiting (33% to 52%), anorexia (35% to 43%), constipation (40%), diarrhea (21% to 39%), decreased appetite (34% to 35%), stomatitis (15% to 33%), gastrointestinal hemorrhage (19% to 24%), dyspepsia (17% to 24%), mucosal inflammation (13% to 15%)

Hematology

• Thrombocytopenia (5% to 58%),  leukopenia (grades 3/4: 37%), neutropenia (12%; grades ≥3: 8% to 27%, grade 4: 27%), bruise (17%), lymphocytopenia (12%)

Musculoskeletal

• Arthralgia (28% to 45%), myalgia (19% to 29%), limb pain (25%), back pain (12% to 21%), dysarthria (8% to 14%)

Renal

• Increased serum creatinine (13% to 16%)

Respiratory

• Upper respiratory tract infection (40% to 47%), cough (26% to 30%), dyspnea (25% to 30%), allergic rhinitis (17%), oropharyngeal pain (16%), sinusitis (7% to 15%), nasal sign and symptoms (mucosal disorder: 14%)

Miscellaneous

• Infection (55%), urinary tract infection (22%), pelvic pain (14%)

Drug Interactions

Pregnancy And Lactation

Pregnancy

Dysregulation of VEGF due to bevacizumab therapy is associated with preeclampsia. Case reports suggest that preeclampsia resolved on discontinuation of bevacizumab.[rx] In addition, VEGF plays a role in maintaining the corpus luteum and amniotic fluid regulation. Hence clinicians should perform a risk-benefit evaluation, and pregnant mothers should be informed regarding the risk of bevacizumab therapy during pregnancy.[rx]

Women of childbearing age should be informed regarding the potential adverse effects of intravitreal bevacizumab on fetal health and should be encouraged to use proper contraceptive methods during treatment. Intravitreal bevacizumab should be avoided, particularly during the first trimester, as susceptibility to teratogens is maximum during organogenesis (3 to 8 weeks postconception).[rx]

Breastfeeding 

Bevacizumab has a high molecular weight, and the concentration in milk is likely to be low. However, VEGF is believed to assist in the maturation of the infant’s gastrointestinal tract; hence use of VEGF inhibitors during breastfeeding is not advised. In addition, there is a lack of clinical data; hence it is recommended that breastfeeding should be stopped during intravenous bevacizumab treatment and for six months after the last dose due to the possibility of serious drug adverse reactions in breastfed infants. Similarly, intravitreal bevacizumab has the most extended half-life of the VEGF inhibitors used in eye disorders, and an alternate intravitreal agent(Aflibercept, ranibizumab) may be preferred.[rx]

• Gastrointestinal perforations: Gastrointestinal (GI) perforations, some fatal, have been seen in patients treated with bevacizumab. It should be discontinued in patients with GI perforations. Most cases occurred within 50 days of treatment initiation. In particular, GI perforations were observed in ovarian cancer patients.[rx] The incidence of GI complications is highest in patients with cervical cancer.[rx][rx] Discontinue bevacizumab in patients who develop gastrointestinal perforation and tracheoesophageal fistula.[rx][rx]

• Hemorrhage: Serious or fatal hemorrhage, including GI bleeding, central nervous system hemorrhage, vaginal bleeding, hemoptysis, and epistaxis, occur up to five times more frequently in patients receiving bevacizumab. These reports have primarily been in non-small cell lung cancer patients with squamous cell histology and a history of hemoptysis (grade ≥2).[rx] Intracranial hemorrhage has been observed in patients previously treated for glioblastoma. The possible mechanism of bevacizumab included disruption of endothelial cell integrity in the tumor microvasculature. Concerns of life-threatening hemorrhage are high, but a retrospective review of 10,598 cancer patients in 57 clinical trials of anti-VEGF treatment, including bevacizumab, indicated that the rate of intracranial hemorrhage in high-grade glioma, and brain metastases, is nominal.[rx]

• Surgery and wound healing complications: Incidents of wound healing and surgical complications (including serious and fatal complications) increase in patients treated with bevacizumab. It should not be given for the 28 days before an elective surgical procedure, at least 28 days following surgery, or until complete healing of the surgical wounds. Necrotizing fasciitis has been documented in patients receiving bevacizumab. Discontinue bevacizumab in patients who develop necrotizing fasciitis.[rx][rx]

• Arterial thromboembolic events (ATE): The risk of cerebral infarction, transient ischemic attacks, myocardial infarction, and angina is higher in patients receiving bevacizumab. In a postmarketing retrospective cohort study involving 2012 patients, acute coronary syndrome and stroke rates were higher two years after intravitreal bevacizumab.[rx]

• Severe hypertension: Hypertension occurs as anti-VEGF therapy causes enhanced expression of the pre-pro ET-1 gene, increasing endothelin-1 and decreasing NO bioavailability. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, and calcium channel blockers are all commonly used to treat bevacizumab-induced hypertension. As NO availability is decreased in patients with VEGF inhibitors-induced hypertension, long-acting oral nitrates have been used for refractory hypertension.[rx]

• Renal injury and proteinuria: As discussed above, nephrotic syndrome and proteinuria are potential complications of bevacizumab therapy. Nephrotic syndrome requires cessation of bevacizumab treatment, while proteinuria needs temporary discontinuation and monitoring.[rx]
• Posterior reversible encephalopathy syndrome (PRES): PRES is a neurological complication characterized by headaches, seizures, visual disturbances, nausea & vomiting associated with hypertension. Discontinuing bevacizumab and blood pressure control is recommended.[rx]
• Ovarian failure:   VEGFA is assumed to play an essential role in regulating angiogenesis in the ovary. The incidence of ovarian failure increases in premenopausal women given bevacizumab. Bevacizumab induces ovarian damage; it is likely that this damage is temporary and disappears within the expected drug clearance in most cases. However, frequent and prolonged drug therapy may complicate the toxicity, and fertility may be temporarily or permanently compromised following bevacizumab administration.[rx]

• Congestive heart failure: Bevacizumab treatment significantly increases cancer patients’ risk of developing CHF. In a meta-analysis, increased risks of developing CHF were observed in patients with breast cancer, renal cell cancer, and glioblastoma. Asymptomatic LVEF dysfunction during bevacizumab therapy should be treated with ACE inhibitors. Discontinuation of bevacizumab is recommended in CHF.[rx][rx]

References