This is an open-label, multicenter Phase I/II study to evaluate the safety and efficacy of AT-101 in combination with docetaxel and prednisone in men with hormone-refractory prostate cancer that are either chemotherapy naive or have received and progressed on a docetaxel containing regimen,

Inclusion Criteria:

1. Rising prostate specific antigen (PSA) despite castrate levels of testosterone due to orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist therapy.
2. Patients must have metastatic disease by bone scan, computed tomography (CT) scan, or magnetic resonance imaging (MRI).
3. ECOG performance status 0 or 1
4. Adequate hematologic function
5. Adequate liver and renal function
6. Able to swallow and retain oral medication.
7. Patients enrolled into Cohort B must have documented progression of disease during treatment with a docetaxel-containing regimen by meeting one or more of the following criteria- rising PSA, progression of disease per RECIST, or >2 new lesions on bone scan.
8. Patients enrolled into Cohort B must have received at least two cycles of docetaxel. Minimum doses of prior docetaxel permitted are 60 mg/m2 on a q 3 week schedule or 20 mg/m2 on a weekly schedule.
9. At least 4 weeks since prior flutamide, megestrol, ketoconazole, and radiotherapy, and at least 6 weeks since prior bicalutamide or nilutamide.

Exclusion Criteria:

1. Patients enrolled into Cohort A must not have received prior chemotherapy for HRPC.
2. Known history of or clinical evidence of central nervous system (CNS) metastases.
3. Active secondary malignancy or history of other malignancy within the last 5 years.
4. Prior history of radiation therapy to > 25% of the bone marrow
5. Peripheral neuropathy of > Grade 2
6. Uncontrolled concurrent illness
7. Failure to recover fully, as judged by the investigator, from prior surgical procedures.
8. Concurrent anti-cancer therapy other than docetaxel and prednisone.
9. Patients must not be receiving concurrent anti-androgen hormonal therapy for HRPC (LHRH therapies are acceptable to maintain castrate levels of testosterone)