Safety and tolerability of local treatment with iloprost, a prostacyclin analogue, in patients with Peyronie's disease: a phase I study

Abstract

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Peyronie's disease (PD) is an acquired curvature of the penis attributable to progressive fibromatosis of the tunica albuginea (TA). It is frequently associated with Dupuytren's contracture and those of Ledderhose. More recently it was found that patients suffering from PD also often suffer from diabetes mellitus and gout. Cigarette smoking and the intake of large amounts of alcohol are considered risk factors for PD.The exact aetiology of the disease is unknown, however, the trauma hypothesis is shared by most authors. According to this theory, repeated sexual microtrauma in people genetically predisposed could cause PD. The inflammatory process leads to the formation of fibrosis and plaques. Plaque can lead to penile curvature and may reduce its functionality. Pain is the most common symptom of early‐stage disease. In the late stages the pain disappears, but erectile dysfunction may occur. Surgical treatment is available, but this exposes the patient to a greater risk of erectile dysfunction and it is most frequently associated with a reduction in the length of the penis. The rationale for local medical therapy is to use a treatment that acts on the initial phase of the disease by reducing and stopping the processes that lead to fibrosis, thus stabilizing the disease. Systemic medical therapy is usually accompanied by high rates of recurrence. Many authors consider local drug therapy more appropriate. Local treatment consists of several types of medication, but results are often sub‐optimal. Anti‐inflammatory or immunoregulatory therapy, either systemic or topical, has shown some efficacy when administered early in the disease by modulating the inflammatory response and attenuating the alteration of tissue repair. Unfortunately, in most cases, patients are first seen when the plaque is chronically inflamed, stabilized and sometimes already calcified. We have tested a biological drug for intralesional administration for the first time. We chose iloprost, an analogue of prostacyclin I2, for its theoretically favourable properties. If used i.v., it has been shown to be effective in treating vascular ischaemic disease such as thromboangioitis obliterans, peripheral arterial occlusive disease, Raynaud's phenomenon and systemic sclerosis. The rationale for the therapeutic use of iloprost in the late stages of PD is based on the assumption that activation of fibrinolysis induced by the drug would be able to determine a regression of the plaque with a consequent reduction of the curvature on erection. The main purpose of this phase I study was to evaluate the safety and tolerability of this drug injected in the context of the fibrous plaque on a small number of patients before designing a large‐scale randomized trial. According to the results,therapy with intralesional iloprost in Peyronie's disease seems to be safe and tolerated and is a possible alternative to surgery. OBJECTIVE To assess the safety and t...

Understanding the course of Peyronie's disease

“…In contrast to the above findings, intralesional injection with verapamil, IFN α‐2b or CCH has shown efficacy in improving penile curvature, reducing plaque size and density, and reducing penile pain . In addition, an initial, non‐controlled study has suggested safety and tolerability of intralesional iloprost in patients with PD; however, further study with placebo comparison is required . Results from a single‐blinded, placebo‐controlled study of 14 men receiving intralesional verapamil over 6 months showed significantly decreased plaque volume compared with placebo (1.42 cm 3 to 0.63 cm 3 in verapamil‐treated men vs. 1.37 cm 3 to 1.39 cm 3 in controls), with a trend towards improvement in penile curvature (mean improvement from pretreatment 37.7° to posttreatment 29.6° in verapamil‐treated patients vs. 33.6° to 31.4° in controls) .…”

Peyronie's disease: What's around the bend?

“…Additional investigational agents for PD treatment include liposomal recombinant human superoxide dismutase (lrhSOD, also known as orgotein),[ 66 67 83 84 85 ] iloprost,[ 87 ] and Peironimev-Plus ® . [ 60 ] The use of intralesional lrhSOD has only been described in observational studies,[ 83 84 85 ] while topical lrhSOD has been evaluated in one observational study[ 66 ] and one crossover RCT with promising results.…”

“…Iloprost is a prostacyclin analog recently tested as a potential intralesional PD therapy, chosen because of its anti-transforming growth factor (TGF)-β activity in fibroblasts. [ 87 ] Additional potentially beneficial effects of prostacyclin include vasodilation, activation of fibrinolysis, and inhibition of platelet function, leukocyte migration, and cell adhesion molecule expression. Improvement in penile curvature was observed in 29% of 38 treated patients, but these data are difficult to interpret given the lack of a placebo comparison group.…”

Pentoxifylline Associated with Other Antioxidants (Multimodal Therapy) on Patients with Peyronie's Disease. Results of a Controlled Study

“…Surgery is indicated when disease is stabilized [12,13] and in patients with severe penile curvature and/or erectile dysfunction [14]. Nonsurgical treatments include: potaba, Vitamin E, colchicine, tamoxifen, propolis, verapamil, interferons, collagenase, cortisone, pentoxifylline, iloprost, iontophoresi, Extracorporeal Shock Wave Therapy (ESWT) and Capacitive Resistive Energy Transfer (Tcare or TECAR therapy) [15][16][17][18][19][20][21]. Since we have already experienced the effectiveness of conservative treatment in the early phase of PD [17,[22][23][24], we implemented a controlled study on patients with PD treated in association with several drugs: Pentoxifylline plus several antioxidants (Vitamin E, blueberries and propolis) and topical Diclofenac.…”