This is a two-arm, randomized Phase II study of intermittent chemotherapy with and without GM-CSF. All patients will receive six 21-day cycles of docetaxel 75 mg/m2 on Day 2 of each cycle and 5 mg prednisone twice a day on Days 1-21. Following six cycles of chemotherapy, eligible subjects will be randomized to no maintenance therapy or to maintenance GM-CSF therapy. The GM-CSF group dose schedule will be 250 mcg/m2 subcutaneous (SQ) daily Days 15-28 every 28 days. Patients in both groups will continue until disease progression at which time GM-CSF will be discontinued and chemotherapy will again be administered.

Inclusion Criteria:

1. Age over 18 years

2. Histologically documented adenocarcinoma of the prostate

3. Progressive metastatic prostate cancer

4. Castrate levels of testosterone (<50 ng/ml) must be maintained

5. Prior hormonal therapy or medications :

   Patients who are receiving an anti-androgen, secondary hormonal therapy (i.e. ketoconazole, aminoglutethimide, megestrol acetate, diethylstilbestrol), 5-alpha reductase inhibitor (i.e. finasteride (Proscar), dutasteride (Avodart)) or herbal prostate medication (i.e. saw palmetto, PC-SPES, PC-PLUS) must discontinue the drug by the date of initiation of chemotherapy on study

6. ≥ 4 weeks since major surgery and fully recovered

7. ≥ 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to ≤grade 1

8. ≥ 8 weeks since the last dose of strontium or samarium

9. Sexually active patients must agree to use adequate contraception

10. Karnofsky Performance Status ≥ 60%

11. Life expectancy >12 weeks

12. Required initial laboratory values Absolute neutrophil count > 1500/ul Platelets > 100,000/ul Hemoglobin > 8.0 g/dl Creatinine ≤ 2.0 X upper limit of normal Bilirubin ≤upper limit of normal (ULN)

aspartate aminotransferase (AST) / alanine aminotransferase (ALT) / alkaline phosphatase: AST AND ALT AND alkaline phosphatase must be within the range allowing for eligibility In determining eligibility, the more abnormal of the 2 values (AST or ALT should be used. An abnormal alkaline phosphatase must be attributed to liver dysfunction and not metastatic bone involvement (i.e elevated gamma-glutamyl transpeptidase (GGTP) or evidence of liver metastases)

Inclusion criteria for late enrolling patients:

1. Age over 18 years
2. Histologically documented adenocarcinoma of the prostate
3. ≤3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to enrollment
4. Docetaxel must have been administered on an every 3 week schedule
5. Each docetaxel dose must have been between 60 and 75 mg/m2
6. Castrate levels of testosterone <50 ng/mL
7. Daily use of other steroids (hydrocortisone, dexamethasone) instead of prednisone or no steroids, is permitted up until time of enrollment
8. A Prostate-specific antigen (PSA) level must have been documented within 6 weeks of initiating docetaxel chemotherapy

Exclusion Criteria:

1. Prior systemic chemotherapy for prostate cancer, other than q 3-week docetaxel/prednisone. Prior neoadjuvant or adjuvant chemotherapy is permitted if there was no evidence of disease relapse within 12 months of the last dose of chemotherapy.
2. >3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered to the patient
3. Peripheral neuropathy >grade 1
4. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support of chemotherapy-related neutropenia is permitted
5. Prior biologic agents (i.e.,anti-angiogenic agents, anti-Epithelial Growth Factor Receptor (EGFR) inhibitors)≤ 4 weeks prior to registration
6. More than two prior therapies with an investigational agent, completed ≤ 4 weeks prior to enrollment (no prior immunotherapeutics are allowed)
7. Myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (NYHA Class III or higher) or uncontrolled cardiac arrhythmia
8. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded
9. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded
10. Poorly controlled diabetes (fasting blood glucose >250) despite optimization of medical therapy

Exclusion criteria for late enrolling patients:

1. Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support for chemotherapy-related neutropenia is permitted
2. Delay of ≥6 weeks between any 2 chemotherapy cycles prior to enrollment on study
3. Cumulative delays ≥8 weeks between chemotherapy cycles prior to enrollment on study