testosterone in treating patients with progressive prostate cancer that no longer responds to hormone therapy

Conditions: Prostate Cancer

Summary: rationale: high doses of testosterone may be effective in killing prostate cancer cells that no longer respond to hormone therapy. purpose: phase i trial to study the effectiveness of testosterone in treating patients who have progressive prostate cancer that no longer responds to hormone therapy.

objectives: * determine the safety and maximum tolerated dose of exogenously administered testosterone in patients with progressive androgen-independent prostate cancer who have been in castrate state either surgically or pharmacologically for a minimum of 1 year. * assess the changes in expression of androgen receptor and other receptors in human biopsy specimens or circulating tumor cells before and after this treatment in this patient population. outline: this is a dose-escalation study. patients receive testosterone via an enhanced absorption transdermal system continuously for 28 days. the transdermal patches are changed daily. cohorts of 3-6 patients receive a fixed daily dose of testosterone with escalating duration of exposure until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities. patients are followed at day 1 and at weeks 2 and 4. projected accrual: a total of 3-18 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed androgen independent metastatic prostate cancer * progressive disease manifested by either: * new osseous lesions by bone scan or a greater than 25% increase in bidimensionally measurable soft tissue disease or the appearance of new sites of disease by mri or ct scan or * minimum of 3 rising psa values from baseline that are obtained 1 week or more apart, or 2 rising psa values more than 1 month apart, where the percentage increase over the range of values is at least 25% * castrate state by orchiectomy or gonadotropin-releasing hormone analogues for minimum of 1 year * testosterone no greater than 30 ng/ml * measurable disease * metastatic disease by bone scan, mri, or ct scan * rising psa values * if receiving antiandrogen therapy, must have shown progressive disease off treatment * no active cns or epidural tumor patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * not specified hematopoietic: * wbc at least 3,500/mm\^3 * platelet count greater than 100,000/mm\^3 hepatic: * bilirubin less than 2.0 mg/dl * sgot less than 3 times upper limit of normal * ptt less than 14 seconds renal: * creatinine less than 2.0 mg/dl or * creatinine clearance greater than 60 ml/min cardiovascular: * no new york heart association class iii or iv cardiac disease pulmonary: * no severe debilitating pulmonary disease other: * no infection requiring iv antibiotics * no other severe medical problems that would increase risk for toxicity prior concurrent therapy: biologic therapy: * recovered from prior biologic therapy * no concurrent immunotherapy chemotherapy: * recovered from prior chemotherapy * no concurrent chemotherapy endocrine therapy: * see disease characteristics * if no prior orchiectomy, must continue on gonadotropin-releasing hormone analogs to maintain castrate levels of testosterone * no concurrent finasteride * no other concurrent hormonal therapy radiotherapy: * recovered from prior radiotherapy * no concurrent radiotherapy to an indicator lesion surgery: * see disease characteristics * recovered from prior surgery * no concurrent surgery on only measurable lesion other: * at least 4 weeks since other prior investigational anticancer drugs and recovered * no other concurrent investigational anticancer agents

Keywords: stage iv prostate cancer recurrent prostate cancer