title: A multicenter phase II study of sunitinib in patients with locally advanced or metastatic differentiated, anaplastic or medullary thyroid carcinomas: mature data from the THYSU study.
abstract: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting.
  
  
  
  This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety.
  
  
  
  Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATC patients and 26 MMTC patients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTC patients and in 38.5% (95% CI: 22.6-56.4) in MMTC patients. No objective response was seen in MATC patients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTC patients, 16.5 and 29.4 months in MMTC patients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths.
  
  
  
  Sunitinib is active in MDTC and MMTC patients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered.
authors.affiliation: Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Clinical Investigational Center, CIC. INSERM CIC 1401, Bordeaux University Hospital, Bordeaux, France; Bordeaux University, Bordeaux, France. Electronic address: alain.ravaud@chu-bordeaux.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.affiliation: Department of Medical Oncology, Centre Leon Bérard, Lyon, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: de la Fouchardière
authors.affiliation: Department of Endocrinology, Toulouse University Hospital, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Caron
authors.affiliation: Methodology Research Unit, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Adelaïde
authors.initials: A
authors.lastname: Doussau
authors.affiliation: Department of Endocrinology, Lille University Hospital, Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Do Cao
authors.affiliation: Methodology Research Unit, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Asselineau
authors.affiliation: Department of Endocrinology, Angers University Hospital, Angers, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Rodien
authors.affiliation: Department of Medical Oncology, Cancer Institute of Montpellier, Montpellier, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Pouessel
authors.affiliation: Department of Endocrinology, Marseille University Hospital, Marseille, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Nicolli-Sire
authors.affiliation: Department of Endocrinology, Nancy University Hospital, Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Endocrinology, Lyon University Hospital, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bournaud-Salinas
authors.affiliation: Department of Endocrinology, Lille University Hospital, Lille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Wemeau
authors.affiliation: Pharmacovigilance Unit, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gimbert
authors.affiliation: Methodology Research Unit, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Marie-Quitterie
authors.initials: MQ
authors.lastname: Picat
authors.affiliation: Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Pedenon
authors.affiliation: Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Digue
authors.affiliation: Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Bordeaux University, Bordeaux, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Daste
authors.affiliation: Department of Endocrinology, Bordeaux University Hospital, Bordeaux, France.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Catargi
authors.affiliation: Department of Medical Oncology, Institut Claudius Régaud, IUCT, Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Delord
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009333:Neck; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Phase II; Sunitinib; Thyroid carcinoma