title: 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 tolerability of intralesional injections of iloprost (an I2 prostacyclin analogue) for its ability to suppress the production of connective tissue growth factor in fibroblasts, for the treatment of Peyronie's disease (PD).
  
  
  METHODS
  A total of 38 patients with PD were preliminarily assessed according to symptoms, the degree of penile curvature and the size and number of plaques. Each patient received weekly intralesional injections of iloprost 200 ng in 1 mL normal saline for 5 weeks. If tolerated, the single dose was increased weekly to the maximum of 400 ng (2 mL). All the patients were preliminarily evaluated using at-home photography and were re-evaluated 2 months after the end of the treatment regimen. There was no placebo control group in this phase I study.
  
  
  RESULTS
  Almost all patients showed mild side effects (burning or pain) during the treatment at the site of injection. All patients tolerated well a iloprost dose of 200 ng; 19 patients reached a 300 ng dose and 14 tolerated a 400 ng dose without showing side effects. A total of 29% of the patients showed an improvement in curvature.
  
  
  CONCLUSIONS
  The results show that therapy with intralesional iloprost is a possible alternative to surgery for Peyronie's disease.
authors.affiliation: Urology Unit, University of Palermo 'P. Giaccone' Policlinic Hospital, Palermo, Italy. uropa@unipa.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Pavone
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Napoli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Caruana
authors.forename: Vincenza
authors.initials: V
authors.lastname: Alonge
authors.forename: Manuela
authors.initials: M
authors.lastname: Usala
authors.forename: Daniela
authors.initials: D
authors.lastname: Abbadessa
mesh_terms: D000328:Adult; D000368:Aged; D011464:Epoprostenol / Q000031:analogs & derivatives*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D010411:Penile Induration / Q000188:drug therapy*
chemical_list: D011464:Epoprostenol; D016285:Iloprost