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brentuximab vedotin (Adcetris)
Structure:
- approximate molecular weight of 153 kDa
- the drug consists of 3 components
a) chimeric IgG1 antibody cAC10, specific for human CD30
b) microtubule disrupting agent MMAE
c) a protease-cleavable linker that covalently attaches MMAE to cAC10
Indications:
- treatment of relapsed or refractory Hodgkin's lymphoma
- treatment of stage III/IV Hodgkin's lymphoma, in combination with doxorubicin, vinblastine, & dacarbazine
- systemic anaplastic large cell lymphoma with treatment failure
Dosage:
- 1.8 mg/kg infused over 30 minutes every 3 weeks
- maximum of 16 cycles
Lyophilyzed powder in single use vials
- reconstituted with 10.5 mL of sterile water yields brentuximab vedotin 5 mg/mL, pH=6.6
Adverse effects:
- hematologic
- neutropenia
- anemia
- thrombocytopenia
- lymphadenopathy
- neurologic
- peripheral neuropathy
- headache
- dizziness
- progressive multifocal leukoencephalopathy [3]
- general
- fatigue
- pyrexia
- chills
- night sweats
- peripheral edema
- anorexia
- weight loss
- infections
- upper respiratory tract infection
- gastrointestinal
- nausea/vomiting
- diarrhea
- abdominal pain
- constipation
- skin
- rash
- pruritus
- alopecia
- dry skin
- respiratory
- cough
- dyspnea
- oropharyngeal
- pulmonary toxicity
- musculoskeletal
- arthralgia
- myalgia
- back pain
- pain in extremity
- muscle spasms
- psychiatric
- insomnia
- anxiety
Mechanism of action:
- antibody-drug conjugate that combines the monoclonal antibody brentuximab & the antimitotic agent monomethyl auristatin (vedotin), thus targeting CD30 receptors on tumor cells before release of the toxic chemotherapeutic agent
General
antineoplastic agent (chemotherapeutic agent)
References
- Waknine Y
Medscape Oncology
FDA Approves Brentuximab for Refractory Lymphomas
http://www.medscape.com/viewarticle/748353
- National Cancer Institute
FDA Approval for Brentuximab Vedotin
http://www.cancer.gov/cancertopics/druginfo/fda-brentuximabvedotin
- FDA MedWatch: 01/13/2012
Adcetris (brentuximab vedotin): Drug Safety Communication -
Progressive Multifocal Leukoencephalopathy and Pulmonary Toxicity
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm287710.htm
- MedPage Today Staff
FDA OKs Adcetris for Untreated Hodgkin's
Brentuximab plus chemo led to better 2-year PFS in ECHELON-1 trial.
MedPage Today. March 20, 2018
https://www.medpagetoday.com/hematologyoncology/lymphoma/71884
- Adcetris
http://www.rxlist.com/adcetris-drug.htm
Component-of
brentuximab vedotin/doxorubicin/vinblastine/dacarbazine (A+AVD)