Neoadjuvant Therapy With Docetaxel and Ketoconazole in Patients With High-Risk Prostate Cancer: A Pilot Study (IST 16167)

Inclusion Criteria:

• Patients must have histologically proven adenocarcinoma of the prostate.

• Patients must meet at least one of the following high risk criteria:

  • PSA > 20
  • Gleason score 8 or greater
  • Presence of pathological Gleason grade 4 or higher as the majority sum on biopsy core
  • Greater than 50% of cores at time of biopsy positive for cancer
  • Clinical Stage T3 Disease
  • Patients must have PS of 0-1(ECOG) and medically deemed a surgical candidate for radical prostatectomy.
  • Age > or = to 18.
  • Patients with a pre-existing peripheral neuropathy of equal to or greater than grade two are ineligible.
  • Serum Creatinine must be < or equal to 2.0mg/dl.
  • Patients must currently not receiving any drug which is metabolized by cytochrome P450-3A4 including the statins, cyclosporin, terfenadine and erythromycin.
  • Prior to receiving any dose of docetaxel, patients should have absolute neutrophil counts > 1,500, hemoglobin > 8.0 g/dl and platelet counts > 100,000/mm3.
  • Patients with bilirubin elevated above institutional upper limit of normal (ULN)must be excluded. Transaminases (SGOT and/or SGPT) may be up to 5.0 x institutional upper limit of normal (ULN) if alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 5 x ULN if transaminases are < ULN. However, patients who have both transaminase elevation > 1.5 x ULN and alkaline phosphatase > 2.5 x ULN are not eligible for this study (due to decrease clearance of docetaxel and increased risk of toxicity).
  • Patients receiving concurrent warfarin are eligible but require monitoring of protime on a weekly basis.
  • Patients with clinical stage T4 disease are not eligible.
  • Patients must not had have received prior treatment with surgery, radiation or hormone deprivation.
  • Patients with other primary malignancies previously treated with chemotherapeutic agents are not eligible.
  • Patients must not have had a history of peptic ulcer disease requiring treatment with surgery or endoscleral.
  • Patients requiring corticosteroids for other systemic diseases are not eligible.
  • Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 are not eligible.
  • All patients must sign informed consent.
  • Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.