• PSA response, defined as the first evidence of a total serum PSA decline of >50% from baseline maintained for at least 28 days and confirmed with two consecutive measurements taken two weeks apart
• Time to sustained biochemical response, defined as the time from first administration of drug to first evidence of sustained response
• Duration of sustained response, defined as time from PSA decrease of >50% from baseline to the first evidence of disease progression
• Overall survival

• PSA response, defined as the first evidence of a total serum PSA decline of >50% from baseline maintained for at least 28 days and confirmed with two consecutive measurements taken two weeks apart [ Time Frame: within the first 3 months ]
• Time to sustained biochemical response, defined as the time from first administration of drug to first evidence of sustained response [ Time Frame: two years ]
• Duration of sustained response, defined as time from PSA decrease of >50% from baseline to the first evidence of disease progression [ Time Frame: two years ]
• Overall survival [ Time Frame: two years ]

The purpose of this study is to evaluate the effect of the combination of mitoxantrone and GM-CSF on time to progression in patients with hormone-refractory prostate cancer.

The purpose of this study is to evaluate the effect of the combination of mitoxantrone and GM-CSF on time to progression in patients with hormone-refractory prostate cancer. To date, there are no curative treatments for prostate cancer that has become hormone-refractory. Treatments appropriate for prostate cancer at this stage include docetaxel, which, in combination with prednisone, has recently been shown to lead to a survival benefit, and mitoxantrone, which, to date, has been shown to lead to a more favorable outcome than steroids alone, but without a survival benefit. GM-CSF is a cytokine that is thought to lead to an enhanced antitumor immune response, presumably through induction of tumor necrosis factor and interleukin-1 expression, as well as growth and proliferation of macrophages and dendritic cells. Both preclinical models and Phase II studies have suggested that GM-CSF as a single agent may have antitumor activity in advanced prostate cancer. To date, the use of GM-CSF for the treatment of prostate cancer has been explored in different contexts, and, more specifically, as a single agent in androgen-independent prostate cancer (AIPC) and hormone-refractory prostate cancer (HRPC), in combination with thalidomide in hormone-naïve prostate cancer and androgen-dependent advanced prostate cancer with ketoconazole in AIPC, and finally with CTLA4 in HRPC. For patients with HRPC who have failed first line chemotherapy, few, non-curative options are available, one of them involving the use of mitoxantrone. On the basis of GM-CSF's mechanism of action, the addition of GM-CSF to a mitoxantrone-containing regimen may lead to enhanced antitumor activity in patients with HRPC.

• Drug: Mitoxantrone
• Drug: GM-CSF

Inclusion Criteria:- must give signed written informed consent

• must be of age 18 years or older
• must have histologically confirmed adenocarcinoma of the prostate
• must have hormone-refractory prostate cancer
• must have failed first-line docetaxel-containing regimen
• must not have had any prior immunotherapy including, but not limited to, vaccines and GM-CSF
• minimum PSA > 5mg/dL, and rising according to the PSA Consensus Criteria (i.e. progressive disease after androgen deprivation and during first-line docetaxel-based chemotherapy)
• KPS > 60%
• Life expectancy of greater than 6 months

Exclusion Criteria:- Concomitant hormonal therapy

• Noncompliance
• Use of herbal products known to decrease PSA levels
• Use of supplements or complementary medicines, except for conventional multivitamin supplements, selenium, lycopene, soy supplements, Vitamin E
• Initiation of bisphosphonates within one month prior to enrollment or throughout the study
• Any prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment
• Major surgery or radiation therapy completed <4 weeks prior to enrollment
• Any concomitant second malignancy other than non-melanoma skin cancer
• Any concomitant serious infection or nonmalignant medical illness
• ANC < 1,500/µl, platelet count <100,000/µl, hemoglobin < 8 mg/dl
• Total bilirubin greater than 1.5 x ULRR
• ALT or AST greater than 2.5 x ULRR if no demonstrable liver metastases or greater than 5.0 x ULRR in presence of liver metastases