PMID- 22327313
OWN - NLM
STAT- MEDLINE
DCOM- 20130403
LR  - 20220311
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 30
IP  - 5
DP  - 2012 Oct
TI  - Antiangiogenic therapy for advanced renal cell carcinoma: management of 
      treatment-related toxicities.
PG  - 2066-79
LID - 10.1007/s10637-012-9796-8 [doi]
AB  - Treatment of metastatic renal cell carcinoma (mRCC) has evolved rapidly over the 
      last two decades as major pathways involved in pathogenesis have been elucidated. 
      These include the vascular endothelial growth factor (VEGF) axis and mammalian 
      target of rapamycin (mTOR). Therapies targeting the VEGF pathway include 
      bevacizumab, sorafenib, sunitinib, pazopanib, and axitinib, whereas temsirolimus 
      and everolimus inhibit the mTOR pathway. All of these novel therapies-VEGF and 
      mTOR inhibitors-are associated with a variety of unique toxicities, some of which 
      may necessitate expert medical management, treatment interruption, or dose 
      reduction. Common adverse events with newer drugs include hypertension, skin 
      reactions, gastrointestinal disturbances, thyroid dysfunction, and fatigue. 
      Skilled management of these toxicities is vital to ensure optimal therapeutic 
      dosing and maximize patient outcomes, including improved survival and quality of 
      life. This review describes and compares the toxicity profiles of novel 
      molecularly targeted agents used in the treatment of mRCC and presents guidance 
      on how best to prevent and manage treatment-related toxicities. Particular 
      attention is given to axitinib, the newest agent to enter the armamentarium. 
      Axitinib is a second-generation receptor tyrosine kinase inhibitor with potent 
      VEGF receptor inhibition that provides durable responses and superior 
      progression-free survival in advanced RCC compared with sorafenib.
FAU - Cohen, Roger B
AU  - Cohen RB
AD  - Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, PA 
      19104, USA. roger.cohen@uphs.upenn.edu
FAU - Oudard, Stephane
AU  - Oudard S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120212
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Angiogenesis Inhibitors/*adverse effects/*therapeutic use
MH  - Carcinoma, Renal Cell/*blood supply/*drug therapy/metabolism
MH  - Humans
MH  - Kidney Neoplasms/*blood supply/*drug therapy/metabolism
MH  - Molecular Targeted Therapy/methods
MH  - Neovascularization, Pathologic/drug therapy
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
PMC - PMC3432793
COIS- Roger Cohen serves as a paid member of a data safety and monitoring committee for 
      a non-oncology Pfizer product. In addition, Dr. Cohen has received past funding 
      from Pfizer for the conduct of clinical trials. These funds were paid to the Fox 
      Chase Cancer Center. Stephane Oudard has received honoraria from Pfizer, 
      Novartis, Roche, and Sanofi-Aventis.
EDAT- 2012/02/14 06:00
MHDA- 2013/04/04 06:00
PMCR- 2012/02/12
CRDT- 2012/02/14 06:00
PHST- 2011/11/28 00:00 [received]
PHST- 2012/01/20 00:00 [accepted]
PHST- 2012/02/14 06:00 [entrez]
PHST- 2012/02/14 06:00 [pubmed]
PHST- 2013/04/04 06:00 [medline]
PHST- 2012/02/12 00:00 [pmc-release]
AID - 9796 [pii]
AID - 10.1007/s10637-012-9796-8 [doi]
PST - ppublish
SO  - Invest New Drugs. 2012 Oct;30(5):2066-79. doi: 10.1007/s10637-012-9796-8. Epub 
      2012 Feb 12.