PMID- 23801303
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20220408
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 31
IP  - 5
DP  - 2013 Oct
TI  - Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast 
      cancer: a randomized Phase II study.
PG  - 1345-54
LID - 10.1007/s10637-013-9991-2 [doi]
AB  - Hormone receptor-positive breast cancer is treated with estrogen inhibitors. 
      Fulvestrant (FASLODEX), an estrogen receptor (ER) antagonist with no known 
      agonist effects, competitively binds, blocks and degrades the ER. Vascular 
      endothelial growth factor (VEGF) may mediate resistance to ER antagonists. 
      Cediranib is a highly potent VEGF signaling inhibitor with activity against all 
      three VEGF receptors. This randomized Phase II study evaluated cediranib plus 
      fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer 
      were eligible. The primary endpoint was progression-free survival (PFS). 
      Secondary endpoints included objective response rate (ORR), duration of response, 
      clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). 
      Patients received cediranib 45 mg/day (n=31) or placebo (n=31) both plus 
      fulvestrant. Demographic/baseline characteristics were well balanced. Patients 
      treated with cediranib had a numerical advantage in PFS (hazard ratio=0.867, 
      P=0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, 
      respectively) vs. placebo, although not statistically significant. CBR was 42 % 
      in both arms. The most common adverse events (AEs) in the cediranib arm were 
      diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade >/= 
      3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 
      10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in 
      the cediranib arm. There was no evidence of a clinically relevant effect of 
      cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical 
      activity in this population, but cediranib 45 mg was not sufficiently well 
      tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy 
      could be considered.
FAU - Hyams, David M
AU  - Hyams DM
AD  - Desert Regional Medical Center Comprehensive Cancer Center, Palm Springs, CA, 
      USA.
FAU - Chan, Arlene
AU  - Chan A
FAU - de Oliveira, Celia
AU  - de Oliveira C
FAU - Snyder, Raymond
AU  - Snyder R
FAU - Vinholes, Jeferson
AU  - Vinholes J
FAU - Audeh, M William
AU  - Audeh MW
FAU - Alencar, Victor M
AU  - Alencar VM
FAU - Lombard, Janine
AU  - Lombard J
FAU - Mookerjee, Bijoyesh
AU  - Mookerjee B
FAU - Xu, John
AU  - Xu J
FAU - Brown, Kathryn
AU  - Brown K
FAU - Klein, Paula
AU  - Klein P
LA  - eng
SI  - ClinicalTrials.gov/NCT00454805
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130626
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolines)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - NQU9IPY4K9 (cediranib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/adverse effects/pharmacokinetics
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Breast Neoplasms/blood/*drug therapy/pathology
MH  - Estradiol/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacokinetics
MH  - Estrogen Antagonists/administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Fibroblast Growth Factor 2/blood
MH  - Fulvestrant
MH  - Humans
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Protein Kinase Inhibitors/administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Quinazolines/administration & dosage/adverse effects/pharmacokinetics
MH  - Vascular Endothelial Growth Factor A/blood
MH  - Vascular Endothelial Growth Factor Receptor-2/blood
MH  - Young Adult
EDAT- 2013/06/27 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/06/27 06:00
PHST- 2013/05/15 00:00 [received]
PHST- 2013/06/12 00:00 [accepted]
PHST- 2013/06/27 06:00 [entrez]
PHST- 2013/06/27 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - 10.1007/s10637-013-9991-2 [doi]
PST - ppublish
SO  - Invest New Drugs. 2013 Oct;31(5):1345-54. doi: 10.1007/s10637-013-9991-2. Epub 
      2013 Jun 26.