Aviptadil (Senatek).

Aviptadil is an injectable formulation of vasoactive intestinal polypeptide (VIP) in combination with the adrenergic drug phentolamine. Aviptadil in combination with phentolamine and sexual stimulation, is expected to provide a new and effective alternative for erectile dysfunction (ED) patients that is essentially free of the troublesome side effects and cumbersome delivery methods which limit the use of other pharmacologic preparations. Aviptadil can be delivered using Senetek's novel and patented autoinjector (Reliaject), which renders the self-injection process exceptionally easy, unobtrusive to perform and helps ensure accurate, safe delivery of the medication [306380]. In July 1997, Senetek filed a PLA with the Danish Medicines Authority [253591] and its third PLA in Ireland for the treatment of moderate-to-severe, organic-based ED [255084]. In September 1997, Senetek filed PLAs seeking approval to market aviptadil in Switzerland, South Africa and New Zealand 1263505]; by April 2000, it had been approved in New Zealand [361039]. All clinical trials were placed on hold in August 1999 after the FDA advised the MCA of safety concerns regarding a competitor's phentolamine mesylate product (Vasomax; Zonagen Inc/Schering-Plough Corp). At this time, the activities to support the registration of aviptadil in the EU were ongoing and were not impacted by the clinical hold [336510]. In March 2000, after review by an independent clinical pharmacotoxicologist company employed by Senetek, the carcinogenicity observed in animal models was deemed to have no relevance as an indicator of carcinogenic risk in humans. This information was passed to the MCA along with an extensive review of all prior company studies and the medical literature supporting the efficacy and safety of phentolamine mesylate [361039]. In July 2000, the FDA upgraded the status of the aviptadil IND to a partial clinical hold, allowing human studies to be conducted in the US with a limited duration of 3 months and total number of doses not exceeding three per week. The FDA also recommended that Senetek conduct a two-year rodent study of aviptadil as a result of previously reported brown adipose tissue proliferations observed in the course of a competitor's rodent study in which phentolamine mesylate was administered daily [373086]. In August 2000, the MCA lifted the hold on trials stating the findings do not represent a significant carcinogenic risk in man [378615]. In October 2000, marketing approval in the UK was granted by the MCA. Regulatory filings in other European countries are underway to seek pan-European approval for aviptadil under the Mutual Recognition Process [385477].

Lower-energy thermotherapy in the treatment of benign prostatic hyperplasia: long-term follow-up results of a multicenter international study.

The purpose of the present study was to evaluate the long-term results of lower-energy transurethral microwave thermotherapy (TUMT) and to determine predictors for a favorable treatment outcome in an international multicenter study. A total of 1092 patients treated between April 1990 and September 1993 in 6 different centers in different countries were evaluated. All patients were treated in a nonblinded, noncontrolled fashion with the Prostatron thermotherapy device using the lower-energy treatment protocol Prostasoft 2.0. Collected data included voiding parameters, Madsen symptom scores, retreatments, types of retreatment, and dates of retreatment. Instrumental retreatment served as the end point for further evaluation. The average age of our patients was 67 years. At baseline the average uroflow rate was 8.7 ml/s. After treatment the improvement in uroflow was 2-3 ml/s. This was maintained for up to 5 years after treatment for the patients remaining in follow-up. The overall improvement in the Madsen symptom score was 5-6 points for these patients. There was no significant difference between the different centers. During follow-up, however, the number of patients remaining in follow-up decreased rapidly. The absolute instrumental retreatment rate appeared to be 26%; however, when patients no longer in follow-up were taken into account, the calculated retreatment rate was 39.6% (Kaplan-Meier survival analysis). Patients undergoing retreatment were younger at baseline and had a higher Madsen score, a bigger prostate, and a greater postvoid residual. No major complication was seen. Lower-energy TUMT gives a sustained objective and subjective improvement in patients with moderate symptoms and a low-grade bladder outflow obstruction. Patients with bigger prostates, severe symptoms, low rates of maximal uroflow, and large residuals are prone to have a higher degree of prostatic obstruction and are not the ideal candidates for this treatment. The absolute instrumental retreatment rate after 5 years was 26%. Moreover, no significant international difference in treatment outcome was found.

Long-term results of lower energy transurethral microwave thermotherapy.

PURPOSE: We evaluate long-term results of lower energy transurethral microwave thermotherapy (Prostasoft 2.0*) and identify pretreatment characteristics that predict a favorable outcome. MATERIALS AND METHODS: Between December 1990 and December 1992, 231 patients with lower urinary tract symptoms were treated with lower energy transurethral microwave thermotherapy. Subjective and objective voiding parameters were collected from medical records and a self-administered questionnaire. Kaplan-Meier plots were constructed to assess the risk of re-treatment. RESULTS: Of the patients 41% underwent invasive re-treatment within 5 years of followup and 17% were re-treated with medication. The re-treatment-free period was somewhat longer in patients with a peak flow rate greater than 10 ml. per second, a Madsen score 15 or less, a post-void residual volume 100 ml. or less and age greater than 65 years at baseline. Prostate volume did not modify the outcome. No incontinence was caused by transurethral microwave thermotherapy, 8% had recurrent urinary tract infection and 8% had retrograde ejaculation. Only 1 patient had a urethral stricture after transurethral microwave thermotherapy. CONCLUSIONS: At 5 years after transurethral microwave thermotherapy 41% of the patients received instrumental treatment. Patients with a lower Madsen score and lower residual volume, and those with higher peak flow and age were somewhat better responders to lower energy transurethral microwave thermotherapy.