1 ng/mL with objective radiographic improvement. Subsequent studies have shown improved response rates to GM-CSF in earlier-stage disease. Dreicer and coworkers5
administered 250 µg of GM-CSF thrice weekly for a total of 24 weeks to 16 men with prostate cancer in a phase II trial. Treatment was halted for biochemical or objective disease progression. Four of 6 hormone-naive patients completed the trial with stable disease, compared with only 3 of 9 with androgen-independent disease. Another phase II trial examined the effect of GM-CSF in a group of 30 patients with biochemical recurrence after localized therapy.6 Patients received 250 µg/m2 of GM-CSF daily for 14 days, followed by 14 days off. Three Inhibitors,research,lifescience,medical of 29 evaluable patients had a greater than 50% decline in PSA levels during treatment, whereas 16 of 29 had a Inhibitors,research,lifescience,medical 2-fold or greater increase in PSA doubling time. Eight of 29 patients remained on study at the time of publication, with at least stable disease for 20 to 32 months. In a follow-up study, 7 of 29 remained on treatment
a median of 5.1 years from initiation of therapy.7 Patients with a long-term response had lower tumor stage, Gleason score, and pretreatment PSA level. Granulocyte-macrophage colony-stimulating factor has been used with other therapies to evaluate overall benefit. Ryan and colleagues8 published a study on 30 men with HRPC, in which all the patients Inhibitors,research,lifescience,medical were given ketoconazole, Inhibitors,research,lifescience,medical hydrocortisone, and 250 µg/m2 of GM-CSF daily on days 15 to 28 of a 28-day cycle. Treatment was continued until disease progression was confirmed. selleck products Interestingly, those without radiographic disease on study initiation had longer times to progression (15.4 months vs 6.9 months). Thalidomide is another agent that has undergone trials in HPRC, in part owing to its purported antiangiogenic activity in vitro. Dreicer and associates9 looked at a combination of GM-CSF and thalidomide
in 22 patients with HRPC. All patients Inhibitors,research,lifescience,medical had a decreased PSA level at 2 weeks, and 5 had a greater than 50% drop. Seven patients completed the 6 months on protocol. Flt3 Ligand Flt3 ligand is a stimulant of a variety of hematopoietic cell types, including dendritic cells. Preclinical and human studies Electron transport chain have demonstrated the ability of Flt3 ligand to increase circulating levels of dendritic cells. Higano and others10 performed a clinical trial of Flt3 ligand in 31 patients with bone scan-negative HRPC. The treatment involved 6 28-day cycles, with administration of the agent daily for the first 14 days of each cycle. The first cycle was divided into a placebo and Flt3 ligand arms to examine safety, and only injection-site reactions were noted. All 21 patients who completed the study had elevations in circulating dendritic cells, and 11 patients had disease stabilization marked by stable or slight decreases in PSA levels.