title: Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation.
abstract: OBJECTIVE
  We conducted a phase II study to assess the efficacy of continuous dosing of sunitinib in patients with flurodeoxyglucose positron emission tomography (FDG-PET)-avid, iodine-refractory well-differentiated thyroid carcinoma (WDTC) and medullary thyroid cancer (MTC) and to assess for early response per FDG-PET.
  
  
  METHODS
  Patients had metastatic, iodine-refractory WDTC or MTC with FDG-PET-avid disease. Sunitinib was administered at 37.5 mg daily on a continuous basis. The primary end point was response rate per Response Evaluation Criteria in Solid Tumors (RECIST). Secondary end points included toxicity, overall survival, and time to progression. We conducted an exploratory analysis of FDG-PET response after 7 days of treatment.
  
  
  RESULTS
  Thirty-five patients were enrolled (7 MTC, 28 WDTC), and 33 patients were evaluable for disease response. The primary end point, objective response rate per RECIST, was 11 patients (31%; 95% confidence interval, 16-47%). There were 1 complete response (3%), 10 partial responses (28%), and 16 patients (46%) with stable disease. Progressive disease was seen in 6 patients (17%). The median time to progression was 12.8 months (95% confidence interval, 8.9 months-not reached). Repeat FDG-PET was done on 22 patients. The median percent change in average standardized uptake values was -11.7%, -13.9%, and 8.6% for patients with RECIST response, stable disease, and progressive disease, respectively. Differences between response categories were statistically significant (P = 0.03). The most common toxicities seen included fatigue (11%), neutropenia (34%), hand/foot syndrome (17%), diarrhea (17%), and leukopenia (31%). One patient on anticoagulation died of gastrointestinal bleeding.
  
  
  CONCLUSIONS
  Continuous administration of sunitinib was effective in patients with iodine-refractory WDTC and MTC. Further study is warranted.
authors.affiliation: Division of Medical Oncology, National Jewish Health, Denver, Colorado, USA.
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Carr
authors.forename: David A
authors.initials: DA
authors.lastname: Mankoff
authors.forename: Bernardo H
authors.initials: BH
authors.lastname: Goulart
authors.forename: Keith D
authors.initials: KD
authors.lastname: Eaton
authors.forename: Peter T
authors.initials: PT
authors.lastname: Capell
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Kell
authors.forename: Julie E
authors.initials: JE
authors.lastname: Bauman
authors.forename: Renato G
authors.initials: RG
authors.lastname: Martins
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D018276:Carcinoma, Medullary / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D002454:Cell Differentiation; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects; D007455:Iodine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049268:Positron-Emission Tomography / Q000379:methods; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D000077210:Sunitinib; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D014055:Tomography, Emission-Computed; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D019788:Fluorodeoxyglucose F18; D007455:Iodine; D000077210:Sunitinib