Hormonal manipulation with toremifene in sporadic desmoid-type fibromatosis

• We analysed patients treated with toremifene for desmoid-type fibromatosis.
• Toremifene is an anti-oestrogen and possibly influences transforming growth factor-beta and β-catenin pathways.
• Toremifene obtained a clinical benefit (CB) in 86% of patients.
• Toremifene obtained CB also after tamoxifen failure.
• Safety profile of toremifene at 180 mg/d was acceptable.

IntroductionMany patients affected by desmoid-type fibromatosis (DF) are treated with a course of hormonal therapy as front line. So far, tamoxifene has been the preferred choice. Toremifene is an anti-oestrogen agent, but possible further mechanisms of action in desmoids are related to its role in regulation of transforming growth factor-beta and β-catenin pathways.Material and methodsWe retrospectively reviewed all patients treated with toremifene between 2005 and 2012 at a reference institution. Indication to toremifene was radiologically progressive disease and/or symptomatic deterioration. Progression-free survival (PFS), clinical benefit (CB) and safety profile were analysed.ResultsForty-four patients were treated with toremifene 180 mg daily, 20 for radiological progression, 16 for pain and 8 for both. In 28 patients, toremifene was offered as front-line therapy, while in 11 after tamoxifen failure. PFS was 89.6% at 2 years. According to Response Evaluation Criteria in Solid Tumours, partial response, stable disease and disease progression were observed in 25%, 65% and 10% of the patients, respectively. Symptomatic relief was obtained in 75% of patients. Median time to response was 4 months. Overall CB was 86%. Adverse events G≥2 according to National Cancer Institute Common Toxicity Criteria were recorded in ten patients.DiscussionPresent series provides evidence to make toremifene an option in patients with DF, even after failure on different hormonal agents. A prospective trial is ongoing to confirm these results.