Reducing Dexamethasone Around Docetaxel Infusion (REDEX)

Leiden University Medical Center (LUMC)

Status and phase: Unknown; Phase 1

Conditions: Breast Cancer; Prostate Cancer

Treatments: Drug: Dexamethasone; Drug: Prednisone

Study type: Interventional

Funder types: Other

Identifiers

NCT02776436

2015-000718-22 (EudraCT Number)

p15.157

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with early breast cancer, or advanced breast cancer or prostate cancer patients receiving docetaxel (minimal 3 cycles monotherapy or in the regimen 4xAC > 4xdocetaxel or 3xFEC>3xdocetaxel or 6xTAC)
• Age ≥18 years
• WHO performance status 0-2
• Adequate bone marrow function: white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
• Adequate liver function: bilirubin ≤1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL (<5 x UNL in case of liver metastases), Alkaline Phosphatase ≤5 x UNL
• Adequate renal function: the calculated creatinine clearance should be ≥50 mL/min
• Survival expectation must be > 3 months
• Written informed consent according to the local Ethics Committee requirements

Exclusion criteria

• Known hypersensitivity for docetaxel, paclitaxel or other chemotherapeutic agent or products containing polysorbate 80 or an earlier experience of anaphylaxis for food, insect bites, medication or another foreign substance.
• Existence of edema of the limbs or trunk or elsewhere localized.
• Active second malignancy
• Diabetes Mellitus
• Serious other diseases such as recent myocardial infarction (last 6 months), clinical signs of cardiac failure or clinically significant arrhythmias
• Female patients who are pregnant or breast-feeding
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 2 patient groups

Breast cancer

Experimental group

Description:

Dose of prophylactic dexamethasone will be reduced as follows: STEP 1: 12 mg dexamethasone per day (8-4mg/day) for 3 days starting 1 day before administration. (n=6) STEP 2: 8mg dexamethasone per day (8mg once a day) for 3 days starting 1 day before administration. (n=6) STEP 3: day -1: 4 mg, day 0: 8 mg, day 1: 4 mg. (n=6) STEP 4: day -1: 0 mg, day 0: 8 mg, day 1: 4 mg. (n=6) STEP 5: day -1: 0 mg, day 0: 8 mg, day 1: 0 mg. (n=6) STEP 6: day -1: 0 mg, day 0: 4 mg, day 1: 0 mg. (n=6)

Treatment:

Drug: Dexamethasone

Prostate cancer

Experimental group

Description:

Dose of prophylactic dexamethasone will be reduced as follows: STEP 1: 2dd 8 mg at 12 and 1 hr before treatment (besides standard prednisone 5mg bid) (n=6) STEP 2: 8mg dexamethasone 1 hour before treatment (and standard prednisone 5mg bid). (n=6) STEP 3: 4mg dexamethasone 1 hour before treatment (and standard prednisone 5mg bid). (n=6) STEP 4: 0mg dexamethasone (only standard prednisone 5mg bid). (n=6)

Treatment:

Drug: Prednisone

Drug: Dexamethasone