Vorinostat

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 28.11.2021

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Synonym(s)

Suberoylanilide hydroxamic acid inhibitor

Definition
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Oral histone deacetylase inhibitor approved by the US Food and Drug Administration in October 2006 for the treatment of patients with refractory advanced cutaneous T-cell lymphoma.

Pharmacodynamics (Effect)
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The effect is based on an inhibition of histone deacetylase; see also histones below). In vitro studies have shown that vorinostat inhibits histone deacetylase (HDAC) even at low concentrations (nanomolar). It is assumed that some cancer cells have an excess of histone deacetylases and thus suppress further cellular processes that regulate apoptosis, among other things. Vorinostat inhibits the effect of this HDAC. It is hoped that this will reduce the activity of the cancer cells; the exact mechanism is currently not fully characterised.

Indication
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Pregnancy/nursing period
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No use during pregnancy and lactation due to lack of data.

Dosage and method of use
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once/day 400 mg/day p.o. (together with a meal).

Undesirable effects
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Described are gastrointestinal (e.g. diarrhoea, stomach complaints), hematological (e.g. anemia, thrombocytopenia), thrombembolic (e.g. pulmonary embolus), cardiac (e.g. QT prolongation) events, fever, anorexia, taste disorders and hyperglycaemia.

Interactions
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  • Prolongation of prothrombin time and INR with simultaneous administration of coumarins.
  • Severe thrombocytopenia and gastrointestinal haemorrhage when administered simultaneously with other histone deacetylase inhibitors (e.g. valproic acid).

Contraindication
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Insufficient data in children and patients with liver and kidney diseases.

Preparations
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Zolinza (Merck)

Note(s)
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Recent studies have evaluated the humanized CCR4 monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, showing a significant benefit in progression-free survival (PFS). In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. The approval was based on the Phase III MAVORIC trial, which compared mogamulizumab to vorinostat, an FDA-approved drug for this indication, in 372 patients. In this study, mogamulizumab was found to have superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat group, with a hazard ratio of 0.53, p<0.001 (Kim YH et al. 2018).

Patientinformation
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Make sure that you drink a sufficient amount of water (at least 2 litres/day)!

Literature
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  1. Grant S et al (2007) Vorinostat. Nat Rev Drug Discov 6: 21-22
  2. Kim YH et al. (2018) Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol19:1192-1204.

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Last updated on: 28.11.2021