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The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study


N/A
18 Years
N/A
Open (Enrolling)
Both
Breast Cancer, Depression, Hot Flashes, Psychosocial Effects of Cancer and Its Treatment

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Trial Information

The Effect of Antidepressants and Gabapentin on Tamoxifen Pharmacokinetics: A Prospective Study


OBJECTIVES:

- To examine the changes in the plasma concentrations of the hydroxylated metabolite,
4-hydroxy tamoxifen, and endoxifen in women with known or at high risk for developing
breast cancer who are receiving selective serotonin reuptake
inhibitor/serotonin-norepinephrine reuptake inhibitor therapy comprising venlafaxine,
citalopram hydrobromide, escitalopram oxalate, gabapentin, or sertraline hydrochloride
for the treatment of hot flashes, depression, or any other medically indicated
condition.

- To evaluate whether genetic variants known to affect the activity of CYP2D6, SULT1A1,
and other drug metabolizing enzymes (e.g., UGT's) involved in the biotransformation of
tamoxifen citrate affect the plasma concentrations of the hydroxylated metabolites,
4-hydroxy tamoxifen and endoxifen.

OUTLINE: This is a multicenter study.

Patients receive oral tamoxifen citrate and concurrent selective serotonin reuptake
inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) therapy comprising oral
venlafaxine, citalopram hydrobromide, escitalopram oxalate, sertraline hydrochloride, or
gabapentin for 8-24 weeks. Treatment continues in the absence of disease progression.

Blood samples are obtained at baseline and after completion of study therapy. Samples are
evaluated by pharmacokinetic analysis to determine the effects of SSRI/SNRI study drugs on
plasma concentrations of tamoxifen and its metabolites. Plasma levels of tamoxifen citrate,
N-desmethyl tamoxifen, 4-OH tamoxifen, and endoxifen are measured using reverse phase high
performance liquid chromatography. Blood samples are also analyzed by CYP2D6 genotyping to
test for CYP2D6 gene variation (i.e., *3, *4, *6, *10, *17, and *41) in genes that encode
tamoxifen-metabolizing enzymes. Additional CYP2D6 alleles, including gene duplication and
gene deletion (*5) are assessed.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Meets 1 of the following criteria:

- Diagnosis of invasive or non-invasive breast cancer

- At high risk for developing breast cancer

- Has been receiving tamoxifen citrate for at least 4 weeks without any breaks either
for the prevention or the adjuvant treatment of invasive or non-invasive breast
cancer at a dose of 20 mg/day

- Planning to begin medical therapy with one of the following drugs, as determined by
physician:

- Venlafaxine

- Citalopram hydrobromide

- Escitalopram oxalate

- Sertraline hydrochloride

- Gabapentin

- Agrees to continue tamoxifen citrate during the proposed minimum study period of 8
weeks

- Known CYP2D6 genotype

- Not known to be a CYP2D6 poor metabolizer (defined as homozygous for one of the
following CYP2D6 null alleles: *3, *4, *5, *6) as determined from the baseline
genotype test

- Estrogen receptor-positive disease (for patients with breast cancer)

PATIENT CHARACTERISTICS:

- Menopausal status not specified

- Life expectancy ≥ 16 weeks

- Willing to return to primary site of enrollment for follow-up, including any of the
following:

- Mayo Clinic Rochester

- Indiana University

- University of Michigan

- Johns Hopkins

- Fairfax-Northern Virginia Hematology-Oncology, PC

- No contraindication for venlafaxine, citalopram hydrobromide, escitalopram oxalate,
gabapentin, or sertraline hydrochloride

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior and no concurrent medications that are known to inhibit
the CYP2D6 system

Type of Study:

Observational

Study Design:

Observational Model: Case Control, Time Perspective: Cross-Sectional

Outcome Measure:

Percent change in plasma concentrations of 4-hydroxy tamoxifen and of endoxifen after ≥ 8 weeks of concurrent administration of tamoxifen citrate and a CYP2D6 inhibitor

Safety Issue:

No

Principal Investigator

Matthew P. Goetz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000585065

NCT ID:

NCT00667121

Start Date:

March 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • Depression
  • Hot Flashes
  • Psychosocial Effects of Cancer and Its Treatment
  • psychosocial effects of cancer and its treatment
  • breast cancer
  • hot flashes
  • depression
  • Breast Neoplasms
  • Depression
  • Depressive Disorder
  • Hot Flashes

Name

Location

Mayo ClinicRochester, Minnesota  55905
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289