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VORINOSTAT CAP,ORAL

Clinical Criteria Summary

Indication

  • Cutaneous T-cell Lymphoma (CTCL)

Inclusion Criteria

  • Stage histological diagnosis of CTCL with advanced disease documented as Stage IIb or higher including Sézary syndrome
  • Documented contraindication or treatment failure of radiotherapy, total skin electron beam therapy, no PUVA, or extracorporeal photopheresis
  • Documented current or prior treatment or treatment failure of interferon-alpha and oral bexarotene
  • Age > 18 years
  • Ability to swallow capsules
  • Adequate hepatic, renal, and hematological function at baseline
  • Prior chemotherapy has been discontinued for at least 3 weeks and the patient has recovered from toxicities of prior therapy; exception in patients with rapidly progressing disease who should be considered for therapy on an individual basis

Exclusion Criteria

  • Hypersensitivity to vorinostat
  • Pregnant women or women intending to become pregnant (Pregnancy Category D)
  • Use for other indications (such as for colorectal cancer) or in combination with other chemotherapeutic agents is not recommended at this time due to insufficient evidence

Dosing

  • 400 mg orally once daily with food
  • For those intolerant to therapy, dose can be reduced to 300 mg daily or further to 300 mg for 5 consecutive days each week

Monitoring

  • Severe thrombocytopenia and gastrointestinal bleeding (reported with concomitant use of vorinostat and other HDAC inhibitors like valproic acid): Monitor platelet count every 2 weeks during the first 2 months
  • Thrombocytopenia and anemia: Doses should be modified or therapy discontinued according to any reductions in platelet counts and/or hemoglobin
  • Discuss appropriate methods of contraception
  • Pre-existing nausea, vomiting, and diarrhea should be adequately controlled before beginning therapy
  • Hypokalemia or hypomagnesemia should be corrected prior to administration; potassium and magnesium should be considered in patients with nausea, vomiting, diarrhea, fluid imbalance or cardiac symptoms
  • QTc prolongation has been reported; close monitoring should occur particularly among patients taking drugs known to prolong the QTc interval
  • Pulmonary embolism and deep vein thrombosis have been reported; physicians should be alert to signs and symptoms, particularly in patients with a prior history of thromboembolic events
  • Prolongation of prothrombin time and increased INR has occurred among some patients taking vorinostat and warfarin concomitantly
  • Serum glucose should be monitored, especially in diabetic patients; adjustment of diet and/or therapy may be necessary

Discontinuation

  • Vorinostat is given until disease progression or intolerance to therapy occurs

Source Documents