title: Hormonal manipulation with toremifene in sporadic desmoid-type fibromatosis.
abstract: BACKGROUND
  Many 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Forty-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.
  
  
  CONCLUSIONS
  Present 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.
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: marco.fiore@istitutotumori.mi.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiore
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Radaelli
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Callegaro
authors.affiliation: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Palassini
authors.affiliation: Department of Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Barisella
authors.affiliation: Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Department of Cancer Medicine, S. Stefano Civil Hospital, Prato, Italy.
authors.forename: Giacomo G
authors.initials: GG
authors.lastname: Baldi
authors.affiliation: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.affiliation: Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Casali
authors.affiliation: Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D018222:Desmoid Tumors / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017312:Toremifene / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D017312:Toremifene
keywords: Aggressive fibromatosis; Desmoid-type fibromatosis; Hormonal therapy; Soft tissue sarcoma; Toremifene