Phase 1 study to evaluate the safety of REducing the prophylactic dose of DEXamethasone around docetaxel infusion in patients with early or advanced breast cancer and prostate cancer.

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.

Primary:
To determine the optimal dose/recommended dose (RD) of pre-medication
dexamethasone around docetaxel infusion.

Secondary:
* Does a dose reduction of prophylactic dexamethasone around the docetaxel
infusion decrease the body*s metabolic response (glucose, insulin, IGF-1) to
dexamethasone?
* Does a dose reduction of prophylactic dexamethasone around the docetaxel
infusion influence chemotherapy induced toxicity?
* Does a dose reduction of prophylactic dexamethasone around the docetaxel
increase the quality of Life?
* Are there single nucleotide polymorphisms in the glucocorticoid receptor
which can predict metabolic response (glucose, insulin, IGF-1) and side
effects?

Side study:
Does dexamethasone influence the pharmacokinetics (PK) of docetaxel?

Multicenter, open label, non-randomized dose de-escalation study

Dose of prophylactic dexamethasone will be reduced as follows:

* EBC and ABC:
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)

* PC:
STEP 1*: 2dd 8 mg at 12 and 1 hr before treatment (n=6)
STEP 2*: 8mg dexamethasone 1 hour before treatment. (n=6)
STEP 3A*: 4mg dexamethasone 1 hour before treatment, with concommitant use of
2dd 5mg prednisone. (n=6)
STEP 3B*: 4mg dexamethasone 1 hour before treatment, without concommitant use
of prednisone . (n=6)

*If a grade III/IV toxicity (fluid retention or hypersensitivity reaction)
occurs in one of the six patients within one cohort, then three additional
patients will be treated at that dose level. If a grade III/IV toxicity (fluid
retention or hypersensitivity reaction) occurs in two of the six or two of the
nine patients, the previous dose level will be chosen as the RD.

The risk for patients that participate in dose levels were dexamethasone is
reduced around the docetaxel infusion, is probably slightly increased for
experiencing hypersensitivity reaction, fluid retention and nausea and
vomiting. However, the risk are acceptable because patients will benefit from
reducing the dose of dexamethasone by reducing its side effects as
manifestation of latent diabetes mellitus, immunosuppression, personality
changes, irritability, euphoria, or mania and mood swings and they might have a
better quality of life.