A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor
A Pharmacokinetic Study of Genistein, a Tyrosine Kinase Inhibitor
Genistein is a natural product found in soy beans; its consumption has been associated with a
 low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase
 inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases
 in cell adhesion in vivo would phenotypically reverse the first step in the metastatic
 cascade, potentially preventing metastasis formation, and is consistent with epidemiologic
 findings. This study seeks to determine the pharmacokinetics of genistein in humans by
 administering a single dose of genistein and performing a pharmacokinetic analysis. Patients
 will be treated with two formulations of genistein (a 43% genistein preparation or a 90%
 preparation). This is a phase I study, and patients will be treated on one of three dosing
 levels. Patients will be randomly assigned to receive one formulation first, followed by a
 washout period, and will then receive the second preparation (i.e. a randomized cross over
 design). Information from this study will be used to optimally design a multiple dose study
 wherein patients will be treated for longer periods of time.
Genistein is a natural product found in soy beans; its consumption has been associated with a
 low incidence of metastatic prostate cancer. Genistein is a known protein-tyrosine kinase
 inhibitor, and in preclinical studies it has been shown to increase cell adhesion. Increases
 in cell adhesion in vivo would phenotypically reverse the first step in the metastatic
 cascade, potentially preventing metastasis formation, and is consistent with epidemiologic
 findings. This study seeks to determine the pharmacokinetics of genistein in humans by
 administering a single dose of genistein and performing a pharmacokinetic analysis. Patients
 will be treated with two formulations of genistein (a 43% genistein preparation or a 90%
 preparation). This is a phase I study, and patients will be treated on one of three dosing
 levels. Patients will be randomly assigned to receive one formulation first, followed by a
 washout period, and will then receive the second preparation (i.e., a randomized cross over
 design). Information from this study will be used to optimally design a multiple dose study
 wherein patients will be treated for longer periods of time. The duration of this study is
 estimated to be about 4 weeks long for each patient.
Must be 18 years old or greater.

 ECOG performance status of 0-1.

 Individuals without a history of cancer are eligible, as are those with a history of
 cancer. Individuals with a history of cancer (excluding non-melanomatous skin cancer ) will
 need to submit their pathology slides for review in the Laboratory of Pathology, NCI.

 Must be able to understand and give informed consent.

 Life expectancy greater than 6 months.

 Hgb greater than or equal to 8.0gm/dl, platelets greater than or equal to
 100,000/microliters, ANC greater than or equal to 1000/microliters, creatinine less than or
 equal to 2.0/mg/dl, SGPT and SGOT less than or equal to 147 and 168 U/L, total bilirubin
 less than or equal to 2 mg/dl (patients with a higher level of bilirubin due to a familial
 defect in bilirubin metabolism will be considered on an individual basis).

 No history of breast cancer.

 No pregnant or breast feeding subjects.

 Must not be HIV positive.

 No history of venous thrombosis within the past year.

 No medical conditions, which, in the opinion of the investigators would jeopardize either
 the patient or the integrity of the data obtained.

 No patients who are currently receiving active therapy for neoplastic disorders. However,
 patients with prostate cancer who are on an LHRH agonist (e.g., Lupron or Zoladex), or who
 have undergone surgical castration, are eligible for study.

 No patients who are on estrogen therapy.

 No patients taking hormonal forms of contraception.

 No patients with a known soy intolerance.