Trial Information

Phase II Study of Granulocyte-Macrophage Colony Stimulating Factor Plus Mitoxantrone for the Treatment of 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.