Safety and Effectiveness Study of Docetaxel and ZD1839 Followed by Removal of the Prostate to Treat Prostate Cancer

Phase II Trial of Neoadjuvant Docetaxel and ZD 1839 (Iressa) Followed by Radical Prostatectomy in Patients With High Risk, Locally Advanced Prostate Cancer

The purpose of this study is to determine the safety and effectiveness of the combination of docetaxel and ZD1839 on destroying prostate cancer before removal of the prostate.

It is recognized that there is a subset of patients who are at high risk for progression despite aggressive treatment of localized disease at the time of detection. The critical issue is in addressing micrometastatic disease that has already developed prior to diagnosis. This study utilizes daily doses of ZD1839 and weekly docetaxel for two cycles prior to radical prostatectomy.

ZD1839 has demonstrated antiproliferative activity against human tumor xenografts and in coadministration with cytotoxic agents against prostate cell lines (PC-3 and TSU-PRI). The combination of ZD1839 and docetaxel has been reported to be feasible with an acceptable toxicity profile.

This phase II, single center trial is specifically targeting those patients with high-risk adenosarcoma of the prostate.

Inclusion Criteria:

• prostate carcinoma: clinical stage T2b-3 or serum PSA>20 ng/ml or Gleason sum score 8-10.
• clinical T2 patients are eligible if endorectal coil MRI shows T3 disease, or Gleason 4+3 cancer in 5 or more biopsies (minimum of 10 biopsies total required)
• ECOG performance status of 0, 1 or 2
• adequate hematological, liver and renal function
• existing peripheral neuropathy < grade 1
• ability to tolerate oral medications.

Exclusion Criteria:

• Concurrent or prior treatment with radiation, cytotoxic, biologic therapy for prostate cancer
• any major surgery within four weeks
• prior hormonal therapy (except finasteride for obstructive voiding symptoms- -evidence of metastatic disease, confirmed by physical examination, computed tomography of the abdomen and pelvis within 45 days and by bone scan within 60 days of signing informed consent