title: A multiinstitutional phase 2 trial of pazopanib monotherapy in advanced anaplastic thyroid cancer.
abstract: OBJECTIVE
  Pazopanib, an inhibitor of kinases including vascular endothelial growth factor receptor, demonstrated impressive activity in progressive metastatic differentiated thyroid cancer, prompting its evaluation in anaplastic thyroid cancer (ATC).
  Preclinical studies, followed by a multicenter single arm phase 2 trial of continuously administered 800 mg pazopanib daily by mouth (designed to provide 90% chance of detecting a response rate of >20% at the 0.10 significance level when the true response rate is >5%), were undertaken. The primary trial end point was Response Evaluation Criteria in Solid Tumors (RECIST) response.
  
  
  RESULTS
  Pazopanib displayed activity in the KTC2 ATC xenograft model, prompting clinical evaluation. Sixteen trial patients were enrolled; 15 were treated: 66.7% were female, median age was 66 yr (range 45-77 yr), and 11 of 15 had progressed through prior systemic therapy. Enrollment was halted, triggered by a stopping rule requiring more than one confirmed RECIST response among the first 14 of 33 potential patients. Four patients required one to two dose reductions; severe toxicities (National Cancer Institute Common Toxicity Criteria-Adverse Events version 3.0 grades >3) were hypertension (13%) and pharyngolaryngeal pain (13%). Treatment was discontinued because of the following: disease progression (12 patients), death due to a possibly treatment-related tumor hemorrhage (one patient), and intolerability (radiation recall tracheitis and uncontrolled hypertension, one patient each). Although transient disease regression was observed in several patients, there were no confirmed RECIST responses. Median time to progression was 62 d; median survival time was 111 d. Two patients are alive with disease 9.9 and 35 months after the registration; 13 died of disease.
  
  
  CONCLUSIONS
  Despite preclinical in vivo activity in ATC, pazopanib has minimal single-agent clinical activity in advanced ATC.
authors: Division of Medical Oncology, Mayo Clinic Rochester, Rochester, Minnesota 55905, USA. bible.keith@mayo.edu
authors: Keith C
authors: KC
authors: Bible
authors: Vera J
authors: VJ
authors: Suman
authors: Michael E
authors: ME
authors: Menefee
authors: Robert C
authors: RC
authors: Smallridge
authors: Julian R
authors: JR
authors: Molina
authors: William J
authors: WJ
authors: Maples
authors: Nina J
authors: NJ
authors: Karlin
authors: Anne M
authors: AM
authors: Traynor
authors: Priya
authors: P
authors: Kumar
authors: Boon Cher
authors: BC
authors: Goh
authors: Wan-Teck
authors: WT
authors: Lim
authors: Ayoko R
authors: AR
authors: Bossou
authors: Crescent R
authors: CR
authors: Isham
authors: Kevin P
authors: KP
authors: Webster
authors: Andrea K
authors: AK
authors: Kukla
authors: Carolyn
authors: C
authors: Bieber
authors: Jill K
authors: JK
authors: Burton
authors: Pamela
authors: P
authors: Harris
authors: Charles
authors: C
authors: Erlichman
mesh_terms: D000368:Aged; D000818:Animals; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib