PMID- 30557850
OWN - NLM
STAT- MEDLINE
DCOM- 20200303
LR  - 20220325
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 26
IP  - 2
DP  - 2019 Feb 1
TI  - Safety and efficacy of two starting doses of vandetanib in advanced medullary 
      thyroid cancer.
PG  - 241-250
LID - ERC-18-0258 [pii]
LID - 10.1530/ERC-18-0258 [doi]
AB  - Vandetanib is an oral tyrosine kinase inhibitor approved for treatment of 
      advanced symptomatic or progressive medullary thyroid cancer (MTC). The current 
      study (Nbib1496313) evaluated the benefit-risk of two starting doses of 
      vandetanib in patients with symptomatic or progressive MTC. Patients were 
      randomized 1:1 to receive vandetanib 150 or 300 mg daily and followed for a 
      maximum of 14 months (Part A), with the option to then enter an open-label phase 
      (Part B) investigating vandetanib 100, 150, 200 and 300 mg daily doses. Efficacy 
      was assessed in Part A, and safety and tolerability during Parts A and B up to 2 
      years post randomization. Eighty-one patients were randomized in Part A and 61 
      patients entered Part B, of whom 37 (60.7%) received 2 years of treatment. 
      Overall, 25% of patients experienced an objective response (OR) at 14 months (OR 
      rate, 0.29 (95% CI, 0.176-0.445) for 300 mg, and 0.20 (95% CI, 0.105-0.348) for 
      150 mg; one-sided P value approximately 0.43). The most common adverse events 
      (AEs) included diarrhea, hypocalcemia, asthenia, QTc prolongation, hypokalemia 
      and keratopathy, all at generally higher incidence with 300 vs 150 mg (Part A). 
      Part B safety and tolerability was consistent with Part A. OR was observed with 
      both vandetanib doses; the 300 mg dose showed a more favorable trend vs 150 mg as 
      initial dose. Thus, for most patients, 300 mg vandetanib is the most appropriate 
      starting dose; dose reductions to manage AEs and lower initial doses for patients 
      with particular comorbidities can be considered.
FAU - Hu, Mimi I
AU  - Hu MI
AD  - Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD 
      Anderson Cancer Center, Houston, Texas, USA.
FAU - Elisei, Rossella
AU  - Elisei R
AD  - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 
      Italy.
FAU - Dedecjus, Marek
AU  - Dedecjus M
AD  - M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, 
      Poland.
FAU - Popovtzer, Aron
AU  - Popovtzer A
AD  - Davidoff Cancer Center, Tel-Aviv University, Petah Tikva, Israel.
FAU - Druce, Maralyn
AU  - Druce M
AD  - William Harvey Research Institute, Barts and the London School of Medicine and 
      Dentistry, London, UK.
FAU - Kapiteijn, Ellen
AU  - Kapiteijn E
AD  - Leiden University Medical Center, Leiden, The Netherlands.
FAU - Pacini, Furio
AU  - Pacini F
AD  - Thyroid Unit, University of Siena, Siena, Italy.
FAU - Locati, Laura
AU  - Locati L
AD  - Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale 
      dei Tumori, Milan, Italy.
FAU - Krajewska, Jolanta
AU  - Krajewska J
AD  - M. Sklodowska-Curie Memorial Institute Cancer Center, Gliwice Branch, Gliwice, 
      Poland.
FAU - Weiss, Richard
AU  - Weiss R
AD  - Sanofi Genzyme, Cambridge, Massachusetts, USA.
FAU - Gagel, Robert F
AU  - Gagel RF
AD  - Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD 
      Anderson Cancer Center, Houston, Texas, USA.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - YO460OQ37K (vandetanib)
RN  - Thyroid cancer, medullary
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Carcinoma, Neuroendocrine/*drug therapy
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Piperidines/*administration & dosage/adverse effects
MH  - Protein Kinase Inhibitors/*administration & dosage/adverse effects
MH  - Quinazolines/*administration & dosage/adverse effects
MH  - Thyroid Neoplasms/*drug therapy
MH  - Young Adult
OTO - NOTNLM
OT  - efficacy
OT  - medullary thyroid cancer
OT  - safety
OT  - vandetanib
EDAT- 2018/12/18 06:00
MHDA- 2020/03/04 06:00
CRDT- 2018/12/18 06:00
PHST- 2018/10/24 00:00 [received]
PHST- 2018/11/12 00:00 [accepted]
PHST- 2018/12/18 06:00 [entrez]
PHST- 2018/12/18 06:00 [pubmed]
PHST- 2020/03/04 06:00 [medline]
AID - ERC-18-0258 [pii]
AID - 10.1530/ERC-18-0258 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2019 Feb 1;26(2):241-250. doi: 10.1530/ERC-18-0258.