PMID- 25102375
OWN - NLM
STAT- MEDLINE
DCOM- 20150615
LR  - 20211021
IS  - 1557-9077 (Electronic)
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 24
IP  - 10
DP  - 2014 Oct
TI  - A phase I study of cabozantinib (XL184) in patients with differentiated thyroid 
      cancer.
PG  - 1508-14
LID - 10.1089/thy.2014.0125 [doi]
AB  - BACKGROUND: Cabozantinib targets tyrosine kinases including MET, vascular 
      endothelial growth factor (VEGF) receptor 2, and rearranged during transfection 
      (RET). Differentiated thyroid cancer (DTC) is a tumor type that may be sensitive 
      to cabozantinib. Therefore, we evaluated cabozantinib in a cohort of heavily 
      pretreated patients with metastatic DTC. METHODS: This single-arm open-label 
      phase I trial assessed the safety, tolerability, and antitumor activity of 
      cabozantinib in DTC patients taking part in a drug-drug interaction study. Adult 
      patients with histologically confirmed metastatic or surgically unresectable DTC 
      (including papillary, follicular, or Hurthle cell) were enrolled. Patients 
      received daily oral dosing of 140 mg cabozantinib. Safety was assessed by 
      evaluation of adverse events (AEs), vital signs, electrocardiograms, laboratory 
      tests, and concomitant medications. Tumor response by magnetic resonance imaging 
      or computed tomography scan was investigator assessed using Response Evaluation 
      Criteria In Solid Tumors (RECIST) v1.0. RESULTS: The study enrolled 15 patients 
      who had failed standard radioactive iodine therapy. Patients had received a 
      median of two prior systemic agents, and 11 patients (73%) had previously 
      received at least one VEGF pathway inhibiting therapy. Common AEs included 
      diarrhea, nausea, fatigue, and decreased appetite. Partial response was reported 
      in eight patients (53%). Median progression-free survival and median overall 
      survival were not reached. CONCLUSIONS: Cabozantinib demonstrates a safety 
      profile similar to other multitargeted VEGFR inhibitors in advanced DTC patients. 
      The antitumor activity observed in this study warrants further investigation of 
      cabozantinib in patients with advanced DTC.
FAU - Cabanillas, Maria E
AU  - Cabanillas ME
AD  - 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of 
      Texas M.D. Anderson Cancer Center , Houston, Texas.
FAU - Brose, Marcia S
AU  - Brose MS
FAU - Holland, Jaymes
AU  - Holland J
FAU - Ferguson, Kimberly C
AU  - Ferguson KC
FAU - Sherman, Steven I
AU  - Sherman SI
LA  - eng
GR  - UL1 TR000371/TR/NCATS NIH HHS/United States
GR  - P30CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
DEP - 20140827
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Anilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 1C39JW444G (cabozantinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Anilides/administration & dosage/adverse effects/*therapeutic use
MH  - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use
MH  - Carcinoma/*drug therapy/enzymology/mortality/secondary
MH  - *Cell Differentiation
MH  - Disease-Free Survival
MH  - Drug Administration Schedule
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic 
      use
MH  - Pyridines/administration & dosage/adverse effects/*therapeutic use
MH  - Thyroid Neoplasms/*drug therapy/enzymology/mortality/pathology
MH  - Time Factors
MH  - Tomography, X-Ray Computed
MH  - Treatment Outcome
MH  - United States
PMC - PMC4195402
EDAT- 2014/08/08 06:00
MHDA- 2015/06/16 06:00
PMCR- 2014/10/01
CRDT- 2014/08/08 06:00
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2015/06/16 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - 10.1089/thy.2014.0125 [pii]
AID - 10.1089/thy.2014.0125 [doi]
PST - ppublish
SO  - Thyroid. 2014 Oct;24(10):1508-14. doi: 10.1089/thy.2014.0125. Epub 2014 Aug 27.