Vandetanib (100 mg) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

被引:201
作者
Robinson, Bruce G. [1 ]
Paz-Ares, Luis [2 ,3 ]
Krebs, Annetta [4 ]
Vasselli, James [4 ]
Haddad, Robert [5 ]
机构
[1] Univ Sydney, Sydney Med Sch, Kolling Inst Med Res, Sydney, NSW 2006, Australia
[2] Inst Biomed Sevilla, Seville 41013, Spain
[3] Hosp Univ Virgen de Rocio, Seville 41013, Spain
[4] AstraZeneca, Wilmington, DE 19850 USA
[5] Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
JAPANESE PATIENTS; EGF-RECEPTOR; PHASE-II; CARCINOMA; ZD6474; HYPOTHYROIDISM; ANGIOGENESIS; EXPRESSION; INHIBITORS; MOTESANIB;
D O I
10.1210/jc.2009-2461
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Patients and Methods: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. Results: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients(53%); the disease control rate was therefore 68%(95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Conclusions: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile. (J Clin Endocrinol Metab 95: 2664-2671, 2010)
引用
收藏
页码:2664 / 2671
页数:8
相关论文
共 29 条
[1]   Medullary thyroid cancer: therapeutic targets and molecular markers [J].
Ball, Douglas W. .
CURRENT OPINION IN ONCOLOGY, 2007, 19 (01) :18-23
[2]   Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features [J].
Bunone, G ;
Vigneri, P ;
Mariani, L ;
Butó, S ;
Collini, P ;
Pilotti, S ;
Pierotti, MA ;
Bongarzone, I .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (06) :1967-1976
[3]  
Carlomagno F, 2002, CANCER RES, V62, P7284
[4]   Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: Results from a phase II study [J].
Cohen, Ezra E. W. ;
Rosen, Lee S. ;
Vokes, Everett E. ;
Kies, Merrill S. ;
Forastiere, Arlene A. ;
Worden, Francis P. ;
Kane, Madeleine A. ;
Sherman, Eric ;
Kim, Sinil ;
Bycott, Paul ;
Tortorici, Michael ;
Shalinsky, David R. ;
Liau, Katherine F. ;
Cohen, Roger B. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (29) :4708-4713
[5]   Inhibition. of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors [J].
Cohen, MS ;
Hussain, HB ;
Moley, JF .
SURGERY, 2002, 132 (06) :960-966
[6]   Imatinib induces hypothyroidism in patients receiving levothyroxinc [J].
de Groot, JWB ;
Zonnenberg, BA ;
Plukker, JTM ;
van Der Graaf, WTA ;
Links, TP .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2005, 78 (04) :433-438
[7]   Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors [J].
Desai, Jayesh ;
Yassa, Leila ;
Marqusee, Ellen ;
George, Suzanne ;
Frates, Mary C. ;
Chen, Ming Hui ;
Morgan, Jeffrey A. ;
Dychter, Samuel S. ;
Larsen, P. Reed ;
Demetri, George D. ;
Alexander, Erik K. .
ANNALS OF INTERNAL MEDICINE, 2006, 145 (09) :660-664
[8]   Progression of medullary thyroid carcinoma:: assessment with calcitonin and carcinoembryonic antigen doubling times [J].
Giraudet, Anne Laure ;
Al Ghulzan, Abir ;
Auperin, Anne ;
Leboulleux, Sophie ;
Chehboun, Ahmed ;
Troalen, Frederic ;
Dromain, Clarisse ;
Lumbroso, Jean ;
Baudin, Eric ;
Schlumberger, Martin .
EUROPEAN JOURNAL OF ENDOCRINOLOGY, 2008, 158 (02) :239-246
[9]   Phase II trial of sorafenib in advanced thyroid cancer [J].
Gupta-Abramson, Vandana ;
Troxel, Andrea B. ;
Nellore, Anoma ;
Puttaswamy, Kanchan ;
Redlinger, Maryann ;
Ransone, Kathy ;
Mandel, Susan J. ;
Flaherty, Keith T. ;
Loevner, Laurie A. ;
O'Dwyer, Peter J. ;
Brose, Marcia S. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (29) :4714-4719
[10]   Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors [J].
Holden, SN ;
Eckhardt, SG ;
Basser, R ;
de Boer, R ;
Rischin, D ;
Green, M ;
Rosenthal, MA ;
Wheeler, C ;
Barge, A ;
Hurwitz, HI .
ANNALS OF ONCOLOGY, 2005, 16 (08) :1391-1397