Treatment of organ confined prostate cancer with third generation cryosurgery: preliminary multicenter experience.

PURPOSE: Cryosurgical ablation of the prostate is 1 approach to the treatment of localized prostate cancer. Third generation cryosurgery uses gas driven probes that allow for a decrease in probe diameter to 17 gauge (1.5 mm). The safety, morbidity and preliminary prostate specific antigen (PSA) results of 122 cases are reported. MATERIALS AND METHODS: A total of 106 patients have undergone percutaneous cryosurgery using a brachytherapy template with at least 12 months of PSA followup. Immediate and delayed morbidities were evaluated. PSA results at 3 and 12 months were recorded, and failure was defined as the inability to reach a nadir of 0.4 ng/ml or less. RESULTS: Complications in patients undergoing primary cryosurgery included tissue sloughing (5%), incontinence (pads, 3%), urge incontinence/no pads (5%), transient urinary retention (3.3%) and rectal discomfort (2.6%). There were no cases of fistulas or infections. Postoperative impotence was 87% in previously potent patients. For patients who underwent salvage cryosurgery there were no fistulas reported and 2 (11%) patients required pads after salvage cryosurgery. A total of 96 (81%) patients achieved a PSA nadir of 0.4 ng/ml or less at 3 months of followup, while 79 of 106 (75%) remained free from biochemical recurrence at 12 months. A total of 42 (78%) low risk patients (Gleason score 7 or less and PSA 10 or less) remained with a PSA of 0.4 ng/ml or less at 12 months of followup, compared to 37 (71%) high risk patients. All patients were discharged within 24 hours. CONCLUSIONS: After a followup of 1 year 3rd generation cryosurgery appears to be well tolerated and minimally invasive. The use of ultrathin needles through a brachytherapy template allows for a simple percutaneous procedure and a relatively short learning curve. A prospective multicenter trial is ongoing to determine the long-term efficacy of this technique.

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer.

PURPOSE: The safety, efficacy and pharmacokinetics of a unique 3-month subcutaneous depot of leuprolide acetate were investigated in patients with prostate cancer. MATERIALS AND METHODS: This open label, noncomparative, 6-month multicenter study enrolled 117 patients diagnosed with adenocarcinoma of the prostate. LA-2550 (22.5 mg. depot) (Atrix Laboratories, Fort Collins, Colorado) was administered subcutaneously once every 3 months. The primary efficacy parameter was serum testosterone 50 ng./dl. or less. Pharmacokinetics were analyzed in a subset of 22 patients. RESULTS: Of the 117 enrolled patients 111 (98%) completed the 6-month study. Five patients withdrew for nontreatment related events and 1 was withdrawn because he received less than a full dose of the study drug. By day 28, 98% of patients had serum testosterone 50 ng./dl. or less and 84% had achieved 20 ng./dl. or less. By day 35 all patients had 50 ng./dl. or less testosterone. A patient with a breakthrough response after testosterone suppression on day 49 (112 ng./dl.) regained suppression (27 ng./dl.) 14 days after the second injection (day 98). At study completion all patients had 50 ng./dl. or less testosterone (mean plus or minus standard error of mean 10.1 +/- 0.07) and 104 of the 111 (94%) had 20 ng./dl. or less. From baseline to month 6 mean luteinizing hormone decreased from 9.2 +/- 1.1 to 0.08 +/- 0.01 mIU/ml. and mean prostate specific antigen decreased more than 98%. No flare reactions were observed and patient assessments of bone pain and urinary symptoms were unchanged. The most common treatment related adverse event was hot flashes, which were mild in 57% of cases, moderate in 12% and severe in 0%. CONCLUSIONS: LA-2550 (22.5 mg. depot) produced and maintained safe and effective suppression of serum testosterone to well below the medical castrate level of 50 ng./dl. or less.