Dexamethasone Regimens for Prophylaxis of Paclitaxel-associated Hypersensitivity Reaction
Condition: Hypersensitivity Reaction
MeSH terms: Hypersensitivity
Study type: Interventional
Phase: Phase 3

Summary: 
      Comparison of the efficacy and side effects of intravenous and oral regimens of dexamethasone
      for prophylaxis of paclitaxel-associated hypersensitivity reactions in primary ovarian,
      fallopian tube and peritoneal cancer patients receiving first cycle of combination paclitaxel
      and carboplatin.
    

Detailed description: 
      The consensus statements on the management of ovarian cancer recommended intravenous
      paclitaxel (175 mg/m2 over 3 hr) plus intravenous carboplatin (area under the curve [AUC]
      5.0-7.5 mg/ml∙min) given every 3 weeks for six cycles for first-line chemotherapy. A major
      limitation of paclitaxel was its poor water solubility, which led to the use of
      polyoxyethylated castor oil vehicle or Cremophor® EL as diluents resulted a hypersensitivity
      reactions (HSRs). Initial P-HSRs generally occur within 10 minutes of the start of paclitaxel
      infusion and most occur with the first or second infusion. Majority of patients manifest as
      minor symptoms characterized by flushing and rashes but sometime life-threatening
      characterized by generalized urticaria, angioedema, bronchospasm and hypertension or until
      fatal may occur. The reaction is likely due to the release of histamine and other vasoactive
      substances in response to Cremophor EL. Originally, the prophylactic regimen composed of the
      use of an oral corticosteroid administered in two doses at 12 and 6 hours prior to paclitaxel
      infusion accompanied with histamine receptor H1 and H2 antagonists administered intravenously
      30 minutes prior to paclitaxel infusion was found to successfully limit P-HSRs denoted as
      "Conventional oral prophylactic regimen".

      While this three-drug prophylactic regimen has been shown to be effective, it can be
      inconvenient for patients because the oral corticosteroid must be taken 12 and 6 hours before
      chemotherapy administration. If the patient forgets to take one or both pretreatment steroid
      doses, it is not clear whether the patient can be safely treated. This led to the
      experimental prophylactic regimen of one dose of intravenous dexamethasone accompanied with
      the H1 and H2 antagonists administered 30 minutes prior to paclitaxel infusion was
      subsequently reported to be equivalent to the regimen of oral dexamethasone denoted as
      "Modified intravenous prophylactic regimen". This intravenous regimen results in lower total
      steroid doses and precludes the issues of compliance.
    

Intervention name(s): Intravenous Dexamethasone; Oral Dexamethasone
Intervention type(s): Drug; Drug
Intervention description(s): Lactose (Placebo) 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and dexamethasone 20 mg (5mg/ml) given intravenously at 30 minutes before paclitaxel infusion; Dexamethasone 20 mg (4 mg/tablet) or 5 tablets given orally at 12 and 6 hours before paclitaxel infusion and 0.9% NaCL (Placebo) 4 ml given intravenously at 30 minutes before paclitaxel infusion
Other intervention name(s): Dexazone; Dexazone
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; BB 1101
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Dexamethasone; Hypersensitivity reaction; Paclitaxel