• Time to Progression - 1st study drug dose to observation of disease progression (increase >25% over baseline PSA on 2 consecutive measurements 2 weeks apart, need for palliative therapy, formation/progression of new bone lesions, or decline of >20% KPS)
  

• 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
  

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.