ArticlesPrednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial
Introduction
Idiopathic retroperitoneal fibrosis is a rare disease, characterised by the presence of a fibroinflammatory tissue that surrounds the abdominal aorta and the iliac arteries, and often entraps the ureters. The idiopathic form accounts for more than two-thirds of all cases of retroperitoneal fibrosis, with the remainder being secondary to different causes, such as drugs, tumours, infections, radiotherapy, and rare forms of histiocytosis such as the Erdheim-Chester disease.1, 2 Idiopathic retroperitoneal fibrosis is histologically characterised by abundant fibrosis and a mononuclear-cell inflammatory infiltrate mainly composed of lymphocytes, plasma cells, and macrophages.3, 4 Clinical manifestations include abdominal or back pain, systemic symptoms (eg, fatigue, weight loss), and, less frequently, constipation, testicular pain, and claudication. Ureteral obstruction occurs in about 60–80% of cases and often causes acute renal failure.5, 6, 7
The treatment of idiopathic retroperitoneal fibrosis is still empirical since no randomised trials have been done so far. Anecdotal cases of spontaneous resolution have been reported,8, 9, 10 and a few patients with asymptomatic disease not affecting adjacent structures might need only monitoring. With the exception of these rare cases, medical treatment is usually necessary in patients with active disease. Glucocorticoids are deemed the mainstay of therapy, but their optimum dose and duration are unknown. They induce rapid symptom remission, reduction in acute-phase reactant values, and often shrinkage of the disease, but they have substantial side-effects.11, 12 These properties make glucocorticoids ideal as induction treatment, provided that an effective maintenance regimen is available. Other immunosuppressive drugs (eg, mycophenolate mofetil, azathioprine)13, 14, 15, 16, 17 have been successfully used together with glucocorticoids, but the superiority of these combination therapies to glucocorticoids alone is still unproven.14
On the basis of the observed benefit in desmoid tumours, which are characterised by fibroblast proliferation, tamoxifen has been used for idiopathic retroperitoneal fibrosis in various case reports and case series.18, 19, 20, 21, 22 Because these cases had a favourable outcome and the drug tolerability was good, tamoxifen has become an attractive therapeutic option for this disease. We compared the efficacy of prednisone with that of tamoxifen in prevention of relapses in patients with newly diagnosed idiopathic retroperitoneal fibrosis who had received induction treatment with prednisone.
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Patients
In this open-label, randomised controlled trial, we enrolled all patients meeting the eligibility criteria, diagnosed at or referred to the Department of Clinical Medicine and Nephrology of Parma Hospital, Parma, Italy, between Oct 1, 2000, and June 30, 2006. Key inclusion criteria were a new diagnosis of idiopathic retroperitoneal fibrosis and an age of 18–85 years; we also enrolled patients with perianeurysmal retroperitoneal fibrosis, since this form is also idiopathic.7, 23 Key exclusion
Results
Of the 40 patients enrolled (figure 1), one was excluded because the diagnosis was revised (this patient was the subject of a case report).31 Of the 39 patients who started induction prednisone therapy, three were excluded. The remaining 36 completed the month of induction prednisone therapy, at the end of which they all achieved symptom remission and normalisation of ESR and CRP values, and were thus randomly assigned to receive prednisone or tamoxifen.
Demographic, clinical, and laboratory
Discussion
This study, the first randomised trial in retroperitoneal fibrosis to our knowledge (panel), compared the efficacy of prednisone and tamoxifen in maintainance of remission in patients who had received induction prednisone therapy. Induction therapy was very effective in obtaining symptom remission and normalisation of acute-phase reactants. Subsequently, we noted that the proportion of patients who developed relapses while being on treatment was significantly higher in the tamoxifen group than
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