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PHARMACOLOGICAL COMPATIBILITY*

Bevacizumab response in colorectal cancer

Bevacizumab is a recombinant monoclonal antibody directed against vascular endothelial growth factor (VEGF) used in the treatment of some neoplastic diseases such as colon cancer, breast cancer, non-small cell lung cancer and renal cell carcinoma. In addition, it is currently in the research phase for other tumor pathologies and ocular pathologies such as MDAA (Macular Degeneration Associated with Age) and diabetic retinopathy.

ACTION MECHANISM

Recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor (VEGF), key mediator of tumor angiogenesis. Bevacizumab blocks the binding of VEGF to its receptors in vascular endothelial cells, inhibiting neo-angiogenesis in some tumors.

CONTRAINDICATIONS

Hypersensitivity to bevacizumab or to products derived from Chinese hamster ovary cells or to other human or humanized recombinant antibodies.

Bevacizumab is contraindicated during pregnancy.

CAUTIONS

cautions should be taken when bevacizumab is prescribed in patients with hepatic impairment and/or renal insufficiency. Also cautions are needed in patients with neutropenia, with a history of hypertension (increased risk of proteinuria), with clinically significant cardiovascular disease (preexisting coronary artery disease or preexisting congestive heart failure), congenital bleeding diathesis, acquired coagulopathy or who are receiving anticoagulants.

There is a risk of gastrointestinal and gallbladder perforation during treatment with bevacizumab that is increased in patients with metastatic colon or rectum carcinoma and cervical cancer; in these cases treatment should be permanently interrupted if a gastrointestinal perforation develops. In patients with cervical cancer there is an increased risk of fistulas between the vagina and any part of the gastrointestinal tract (gastrointestinal-vaginal fistulas).

Precautions should be taken in patients with hypertension (monitor blood pressure), in cases of arterial thromboembolism (higher in combination with chemotherapy or over 65 years of age), in venous thromboembolic events (including pulmonary embolism), in patients at risk of hemorrhage (hemorrhage associated with the tumor) and in patients with a reaction to perfusion or hypersensitivity. There is an increased risk of pulmonary severe hemorrhage/hemoptysis in non-small cell lung cancer patients.

Treatment with bevacizumab is not recommended in children and adolescents (do not use in 3-18 years old children with high-grade recurrent or progressive glioma).

Bevacizumab can affect women’s fertility (use contraceptive methods during and up to 6 months after treatment).

It is recommended to interrupt treatment and immediately initiate appropriate treatment in those patients who are diagnosed with necrotizing fasciitis.

SIDE EFFECTS

Very common side effects: neutropenia, leukopenia, thrombocytopenia and febrile neutropenia, hypertension (which may require treatment), peripheral sensory neuropathy, anorexia, asthenia, fatigue, diarrhea, nausea, vomiting.

Common side effects: proteinuria, hemorrhage (hemoptysis, mucocutaneous or epistaxis, sometimes intra or peritumoral); arterial thrombosis (cerebrovascular accident, acute myocardial infarction, transient ischemic attack), venous thrombosis (deep vein thrombosis, pulmonary thromboembolism or thrombophlebitis); congestive heart failure, cardiomyopathy, gastrointestinal perforation, pain in the place of injection, diarrhea, abdominal pain, dermatitis, delayed healing of wounds.

Bevacizumab can also cause vitiligo, analytic abnormalities (neutropenia, proteinuria, hypokalemia, hypophosphatemia, increased alkaline phosphatase, usually attributable to the chemotherapy with which bevacizumab is coadministered).

Cases of reversible posterior leukoencephalopathy syndrome (RPLS) and cases of maxillary osteonecrosis have been identified, especially in patients previously treated with bisphosphonates.

PHARMACOLOGICAL INTERACTIONS

Risk of increased severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia (even fatal) in concomitant treatment with platinum and taxanes.

The joint treatment of bevacizumab together with monoclonal antibodies directed to EGFR, such as panitumumab and cetuximab plus chemotherapy, are associated with a decrease in progression-free survival (PFS) and/or with overall survival (OS) and with an increase in toxicity, when compared to only bevacizumab plus chemotherapy regimens.

Microangiopathic hemolytic anemia has been reported in patients treated with the combination of bevacizumab (10 mg/kg every two weeks) and sunitinib maleate (50 mg daily).

The safety and efficacy of the concomitant administration of radiotherapy plus bevacizumab has not been established yet.

BRAND NAME

  • Avastin ®

GENE OR REGION STUDIED


  • VEGFA
  • CXCR4
  • VDBP

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