ketoconazole, hydrocortisone, and gm-csf in treating patients with progressive prostate cancer after hormone therapy

Conditions: Prostate Cancer

Summary: rationale: androgens can cause the growth of prostate cancer cells. drugs, such as ketoconazole, may stop the adrenal glands from making androgens. gm-csf may help ketoconazole work better by making tumor cells more sensitive to the drug. giving ketoconazole together with hydrocortisone and gm-csf may be an effective treatment for prostate cancer. purpose: this phase ii trial is studying how well giving ketoconazole together with hydrocortisone and gm-csf works in treating patients with progressive prostate cancer after hormone therapy.

objectives: primary * evaluate the effect of ketoconazole, hydrocortisone, and sargramostim (gm-csf) on time to clinical progression in patients with prostate cancer that has progressed on primary hormonal therapy. secondary * evaluate the objective response frequency in patients treated with this regimen. * investigate the safety of this regimen. outline: this is an open-label, nonrandomized study. patients receive oral ketoconazole three times daily and oral hydrocortisone twice daily on days 1-28 and sargramostim (gm-csf) subcutaneously on days 15-28. treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. projected accrual: a total of 48 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed adenocarcinoma of the prostate * progressive disease after androgen deprivation and meets 1 of the following criteria: * measurable disease * measurable lesions ≥ 10 mm with spiral ct * up to 5 lesions per organ and 10 lesions total should be identified as target lesions * no measurable disease * patients with prostate-specific antigen (psa)-only disease must have an elevated psa * psa evidence for progressive disease consists of a psa level of ≥ 5 ng/ml that has risen on ≥ 2 successive occasions, ≥ 2 weeks apart * patients with a positive bone scan must also have an elevated psa * patients who received prior antiandrogen as a part of primary androgen ablation therapy must demonstrate disease progression after discontinuation of the antiandrogen * disease progression after antiandrogen withdrawal is defined as 2 consecutive rising psa values obtained ≥ 2 weeks apart, or documented osseous or soft tissue progression * patients receiving flutamide must have had ≥ 1 of the psa values obtained ≥ 4 weeks after flutamide discontinuation * patients receiving bicalutamide or nilutamide must have had ≥ 1 of the psa values obtained ≥ 6 weeks after antiandrogen discontinuation * testosterone \< 50 ng/dl * psa ≥ 5 ng/ml patient characteristics: * karnofsky performance status 60-100% * no serious intercurrent infections or nonmalignant uncontrolled medical illnesses * no psychiatric illnesses or social situations that would limit compliance * no active or uncontrolled autoimmune disease * alt and ast normal * bilirubin normal * absolute neutrophil count ≥ 1,500/mm³ * platelet count ≥ 100,000/mm³ * creatinine ≤ 1.5 times upper limit or normal (uln) * hemoglobin ≥ 8 g/dl * no other currently active malignancy except for nonmelanoma skin cancer * no currently active malignancy defined as therapy completed with ≤ 30% risk of relapse prior concurrent therapy: * see disease characteristics * patients must continue primary androgen deprivation therapy with a luteinizing-hormone releasing-hormone (lhrh) analogue if they have not undergone orchiectomy * no prior systemic chemotherapy for prostate cancer * all other systemic chemotherapy must have been completed ≥ 2 years prior to study * no other concurrent chemotherapy, immunotherapy, or radiotherapy * major surgery or radiation therapy completed ≥ 4 weeks prior to study * no other concurrent corticosteroids, including routine use antiemetics * no prior ketoconazole, aminoglutethimide, or corticosteroids for treatment of progressive prostate cancer * no prior immunotherapy (e.g., vaccines or sargramostim gm-csf) * patients receiving any other hormonal therapy (e.g., megestrol, finasteride, herbal product known to decrease psa levels \[e.g., saw palmetto or pc-spes\], or any systemic corticosteroid) must discontinue the agent ≥ 4 weeks prior to enrollment and progressive disease must be documented after discontinuation * no initiation of bisphosphonate therapy within 1 month prior to starting study therapy * patients on stable doses that show tumor progression are allowed to continue bisphosphonate * no concurrent supplements or complementary medicines/botanicals, except any combination of the following: * conventional multivitamin supplements * selenium * lycopene * soy supplements * vitamin e * at least 8 weeks since prior radiopharmaceuticals (strontium chloride sr 89, samarium sm 153 lexidronam pentasodium) * no other concurrent investigational or commercial anticancer agents or therapies

Keywords: adenocarcinoma of the prostate recurrent prostate cancer