Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies.

Efficacy and safety of testosterone gel 2% (TG) were evaluated in two phase 3, open-labelled, single-arm, multicentre studies (000023 and extension study 000077). Hypogonadal men having serum testosterone levels <300 ng/dl at two consecutive measurements were included. Study duration was 9 months (000023: 3 months; 000077: 6 months). Starting dose of TG (46 mg) was applied on upper arm/shoulder. The primary endpoint (000023) was responder rate (subjects with average 24-hour serum testosterone concentration 300-1050 ng/dl on Day 90). Study 000077 evaluated the safety of TG in patients rolling over from study 000023 over a period of 6 months. Of 180 subjects in 000023, 172 completed and 145 rolled over to 000077, with 127 completers. The responder rate was 85.5%. Fewer subjects in 000077 (12.7%) versus 000023 (31.8%) had maximum testosterone concentration (Cmax ) >1500 ng/dl, with no significant safety concerns. Significant improvements in sexual function and quality of life were noted in both studies. Subjects experienced few skin reactions without notable increases in prostate-specific antigen and haematocrit levels. TG was efficacious with an acceptable safety profile. Cmax >1500 ng/dl did not exhibit distinct impact on safety parameters. However, further optimisation of titration schema to reduce Cmax is warranted while maintaining the average steady state total testosterone concentration.

Long-term survival and biomarker correlates of tasquinimod efficacy in a multicenter randomized study of men with minimally symptomatic metastatic castration-resistant prostate cancer.

PURPOSE: Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial. EXPERIMENTAL DESIGN: Two hundred and one (134 tasquinimod and 67 placebo) men with mCRPC were evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS). RESULTS: With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35-0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42-0.97; P = 0.034) for OS, favoring tasquinimod. Time-to-symptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit. CONCLUSIONS: The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio.

An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction.

AIM: Determine the long-term efficacy, safety and tolerability of avanafil, a highly specific, rapidly absorbed phosphodiesterase type 5 inhibitor in male patients with mild to severe erectile dysfunction (ED), with or without diabetes. METHODS: This was a 52-week, open-label extension of two 12-week, randomised, placebo-controlled, phase 3 trials. Patients were assigned to avanafil 100 mg, but could request 200 mg (for increased efficacy; '100/200-mg' group) or 50 mg (for improved tolerability). Primary end points included percentage of sexual attempts ending in successful vaginal penetration [Sexual Encounter Profile 2 (SEP2)] and intercourse (SEP3) and erectile function domain score per the International Index of Erectile Function (IIEF-EF). RESULTS: Some 712 patients enrolled; 686 were included in the intent to treat population and contributed to the data. All primary end points showed sustained improvement. SEP2 and SEP3 success rates improved from 44% to 83% and from 13% to 68% (100-mg group) and from 43% to 79% and from 11% to 66% (100/200-mg group), respectively. Mean IIEF-EF domain scores improved from 13.6 to 22.2 (100-mg group) and from 11.9 to 22.7 (100/200-mg group). Avanafil was effective in some patients ≤ 15 min and > 6 h postdose. Sixty-five per cent (112/172) of 'nonresponders' to avanafil 100 mg responded to the 200-mg dose. The most common (≥ 2%) treatment-emergent adverse events were headache, flushing, nasopharyngitis and nasal congestion; < 3% of patients discontinued therapy because of adverse events. CONCLUSIONS: The long-term tolerability and improvement in sexual function, coupled with rapid onset, suggest that avanafil is well suited for the on-demand treatment of ED.

Transurethral microwave hyperthermia in the treatment of chronic nonbacterial prostatitis.

Chronic nonbacterial prostatitis is an ill-understood and difficult-to-diagnose disease. Symptoms of chronic nonbacterial prostatitis are similar to those of chronic prostatitis and include low back pain, frequency, dysuria, perineal discomfort, and painful ejaculation. In view of uncertainty about etiology, treatment of chronic nonbacterial prostatitis remains speculative. Most treatment is aimed at relieving symptoms and not at curing the disease. Because of the troublesome nature of chronic nonbacterial prostatitis and the poor results obtained from traditional treatment methods, a new modality of transurethral microwave hyperthermia was investigated. Six patients were treated from January 1994 through June 1995 by use of transurethral microwave hyperthermia. These men were treated four times during a 2-week period. Their average symptom score decrease was 74.9% and was associated with minimal morbidity. Based on this result, it is concluded that transurethral microwave hyperthermia is a safe and effective treatment modality for chronic nonbacterial prostatitis.

Metastatic Sertoli cell carcinoma of the testis.

Metastatic Sertoli cell tumor is a very rare and deadly disease accounting for approximately 1% of all testicular carcinomas. With fewer than 30 cases reported in the literature, there has not been a uniform treatment regimen with good results. Retroperitoneal lymph node dissection, chemotherapy, and radiation therapy in combination appear to offer the best outcome. This report describes the occurrence of this rare tumor in a 38-year-old man 2 years after left orchiectomy.

Early detection of stage A prostate carcinoma: combined use of prostate-specific antigen and transrectal ultrasonography.

We prospectively studied 103 men who had normal results on digital prostate examinations but had bladder outlet obstruction secondary to prostatic hypertrophy and needed transurethral prostatectomy. All men underwent a preoperative transrectal ultrasonographic examination of the prostate and prostate-specific antigen (PSA) level determination. A total of 30 cancers were ultimately detected, 22 (73%) of which were detected preoperatively by either an abnormal ultrasonogram or elevated PSA levels (or both). Eight of these men were spared transurethral prostatectomy and had definitive treatment based on transrectal biopsy and appropriate staging evaluation. For PSA and ultrasonography combined, the sensitivities and negative predictive values for cancer (92% and 94%, respectively) were superior to the specificities and positive predictive values (71% and 64%, respectively). The combined use of both studies is recommended to rule out cancer in candidates for prostatectomy but not to routinely screen the general male population older than 40 years.

Priapism associated with intranasal cocaine abuse.

Cocaine abuse has escalated to epidemic proportions in the United States. In addition to the social and economic problems associated with the recreational use of this agent, a variety of medical complications have been reported. The occurrence of priapism with intranasal use has not been documented previously. We report a case of priapism secondary to intranasal cocaine abuse and describe the possible neurochemical etiology for this phenomenon.