The manufacturer recommends two different regimens of prophylactic dexamethasone to prevent hypersensitivity and fluid retention reactions caused by docetaxel: a 3-day regime of dexamethasone 8mg twice a day starting the day before chemotherapy for breast cancer and for prostate cancer 3 times 8mg dexamethasone on the day of docetaxel infusion, given the concurrent use of prednisone 2dd5mg. There is little evidence that supports this high dose regimen used nowadays. There is need to re-evaluate this high dosage of dexamethasone for three main reasons. First, dexamethasone can give side effects such as manifestation of latent diabetes mellitus, immunosuppression, personality changes, irritability, euphoria, or mania and mood swings. Second, dexamethasone is an immune suppressor, which might inhibit chemotherapy-induced apoptosis and compromise the efficacy of chemotherapeutic agents. Third, dexamethasone is a CYP3A4 inducer, which might increase docetaxel clearance. This study aims to evaluate the feasibility of reducing prophylactic of dexamethasone around docetaxel infusion.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Dose of prophylactic dexamethasone will be reduced for all patients
standard prednisone 5 mg bid for patients with prostate cancer
Reinier de Graaf hospital
Delft, Netherlands
Leiden university medical center
Leiden, Netherlands
Haga hospital
The Hague, Netherlands
Optimal dose/recommended dose (RD) of pre-medication dexamethasone around docetaxel infusion, dependent of occurrence of grade III/IV fluid retention and HSR according to the NCI CTCAE v4.03.
If one grade III/IV HSR or fluid retention reaction occurs in one of the six patients within one cohort, then three additional patients will be treated at that dose level. If there are no additional grade III/IV HSR or fluid retention in that additional 3 patients accrual to the next lower dose level will be started. If a grade III/IV HSR or fluid retention occurs in at least 2/6 or 2/9 patients, that dose will not be tolerated as safe and the last previous dose level of dexamethasone will be the RD.
Time frame: up to 30 weeks
Glucose (mmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time frame: up to 30 weeks
Insulin(mU/L), response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time frame: up to 30 weeks
IGF-1(nmol/L) response due to prophylactic dexamethasone on day 0 before chemotherapy.
Time frame: up to 30 weeks
Number of participants with toxicity of chemotherapy according to NCI CTCAE v4.03 compared in each dose level of dexamethasone.
Time frame: up to 30 weeks
Patient's quality of life (descriptive).
Time frame: up to 30 weeks
Number of patients with single nucleotide polymorphisms in the glucocorticoid receptor.
Time frame: one week
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