title: A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H.
abstract: BACKGROUND
  Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). OBJECTIVE, DESIGN, SETTING, PATIENTS, INTERVENTION, AND OUTCOME MEASURES: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability.
  
  
  RESULTS
  From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related.
  
  
  CONCLUSIONS
  Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.
authors.affiliation: Division of Medical Oncology (K.C.B., J.R.M., J.R., K.S., J.K.B., K.P.W., C.R.I., C.E.), Division of Biomedical Statistics and Informatics (V.J.S.), Division of Endocrinology (J.C.M., B.M., I.H., V.F.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (R.C.S.), Division of Medical Oncology (W.J.M., M.E.M., C.B.), Mayo Clinic Florida, Jacksonville, Florida 32224; Division of Medical Oncology (N.K.), Mayo Clinic Arizona, Scottsdale, Arizona 85259; Carbone Cancer Center (A.M.T.), University of Wisconsin, Madison Wisconsin 53705; Minnesota Oncology Hematology (P.J.F.), PA, Minneapolis, Minnesota 55407; National University Hospital (C.G.), Singapore 119228; and Cancer Therapy Evaluation Program (P.H.), National Cancer Institute, Bethesda, Maryland 20892.
authors.forename: Keith C
authors.initials: KC
authors.lastname: Bible
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Julian R
authors.initials: JR
authors.lastname: Molina
authors.forename: Robert C
authors.initials: RC
authors.lastname: Smallridge
authors.forename: William J
authors.initials: WJ
authors.lastname: Maples
authors.forename: Michael E
authors.initials: ME
authors.lastname: Menefee
authors.forename: Joseph
authors.initials: J
authors.lastname: Rubin
authors.forename: Nina
authors.initials: N
authors.lastname: Karlin
authors.forename: Kostandinos
authors.initials: K
authors.lastname: Sideras
authors.forename: John C
authors.initials: JC
authors.lastname: Morris
authors.forename: Bryan
authors.initials: B
authors.lastname: McIver
authors.forename: Ian
authors.initials: I
authors.lastname: Hay
authors.forename: Vahab
authors.initials: V
authors.lastname: Fatourechi
authors.forename: Jill K
authors.initials: JK
authors.lastname: Burton
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Webster
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bieber
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Boon
authors.initials: B
authors.lastname: Cher Goh
authors.forename: Crescent R
authors.initials: CR
authors.lastname: Isham
authors.forename: Pamela
authors.initials: P
authors.lastname: Harris
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040262:Receptors, Vascular Endothelial Growth Factor