PMID- 23514360
OWN - NLM
STAT- MEDLINE
DCOM- 20130916
LR  - 20221207
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 13
DP  - 2013 Mar 21
TI  - Safety and efficacy of everolimus in Chinese patients with metastatic renal cell 
      carcinoma resistant to vascular endothelial growth factor receptor-tyrosine 
      kinase inhibitor therapy: an open-label phase 1b study.
PG  - 136
LID - 10.1186/1471-2407-13-136 [doi]
AB  - BACKGROUND: In China, there are currently no approved therapies for the treatment 
      of metastatic renal cell carcinoma (mRCC) following progression with vascular 
      endothelial growth factor (VEGF)-targeted agents. In the phase 3 RECORD-1 trial, 
      the mammalian target of rapamycin (mTOR) inhibitor everolimus afforded clinical 
      benefit with good tolerability in Western patients with mRCC whose disease had 
      progressed despite VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. 
      This phase 1b study was designed to further evaluate the safety and efficacy of 
      everolimus in VEGFr-TKI-refractory Chinese patients with mRCC. METHODS: An 
      open-label, multicenter phase 1b study enrolled Chinese patients with mRCC who 
      were intolerant to, or progressed on, previous VEGFr-TKI therapy (N = 64). 
      Patients received everolimus 10 mg daily until objective tumor progression 
      (according to RECIST, version 1.0), unacceptable toxicity, death, or study 
      discontinuation for any other reason. The final data analysis cut-off date was 
      November 30, 2011. RESULTS: A total of 64 patients were included in the study. 
      Median age was 52 years (range, 19-75 years) and 69% of patients were male. 
      Median duration of everolimus therapy was 4.1 months (range, 0.0-16.1 months). 
      Expected known class-effect toxicities related to mTOR inhibitor therapy were 
      observed, including anemia (64%), hypertriglyceridemia (55%), mouth ulceration 
      (53%), hyperglycemia (52%), hypercholesterolemia (50%), and pulmonary events 
      (31%). Common grade 3/4 adverse events were anemia (20%), hyperglycemia (13%), 
      increased gamma-glutamyltransferase (11%), hyponatremia (8%), dyspnea (8%), 
      hypertriglyceridemia (6%), and lymphopenia (6%). Median PFS was 6.9 months (95% 
      CI, 3.7-12.5 months) and the overall tumor response rate was 5% (95% CI, 1-13%). 
      The majority of patients (61%) had stable disease as their best overall tumor 
      response. CONCLUSIONS: Safety and efficacy results were comparable to those of 
      the RECORD-1 trial. Everolimus is generally well tolerated and provides clinical 
      benefit to Chinese patients with anti-VEGF-refractory mRCC. TRIAL REGISTRATION: 
      clinicaltrials.gov, NCT01152801.
FAU - Guo, Jun
AU  - Guo J
AD  - Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Beijing 
      100142, China. guoj307@126.com
FAU - Huang, Yiran
AU  - Huang Y
FAU - Zhang, Xu
AU  - Zhang X
FAU - Zhou, Fangjian
AU  - Zhou F
FAU - Sun, Yinghao
AU  - Sun Y
FAU - Qin, Shukui
AU  - Qin S
FAU - Ye, Zhangqun
AU  - Ye Z
FAU - Wang, Hui
AU  - Wang H
FAU - Jappe, Annette
AU  - Jappe A
FAU - Straub, Patrick
AU  - Straub P
FAU - Pirotta, Nicoletta
AU  - Pirotta N
FAU - Gogov, Sven
AU  - Gogov S
LA  - eng
SI  - ClinicalTrials.gov/NCT01152801
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130321
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Asian People
MH  - Carcinoma, Renal Cell/*drug therapy/mortality/*pathology
MH  - China
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/mortality/*pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Neoplasm Metastasis
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors
MH  - Sirolimus/*analogs & derivatives/pharmacology/therapeutic use
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC3626915
EDAT- 2013/03/22 06:00
MHDA- 2013/09/17 06:00
PMCR- 2013/03/21
CRDT- 2013/03/22 06:00
PHST- 2012/09/18 00:00 [received]
PHST- 2013/03/11 00:00 [accepted]
PHST- 2013/03/22 06:00 [entrez]
PHST- 2013/03/22 06:00 [pubmed]
PHST- 2013/09/17 06:00 [medline]
PHST- 2013/03/21 00:00 [pmc-release]
AID - 1471-2407-13-136 [pii]
AID - 10.1186/1471-2407-13-136 [doi]
PST - epublish
SO  - BMC Cancer. 2013 Mar 21;13:136. doi: 10.1186/1471-2407-13-136.