PMID- 23572408
OWN - NLM
STAT- MEDLINE
DCOM- 20140203
LR  - 20220310
IS  - 1179-1950 (Electronic)
IS  - 0012-6667 (Linking)
VI  - 73
IP  - 5
DP  - 2013 Apr
TI  - Optimal management of metastatic renal cell carcinoma: current status.
PG  - 427-38
LID - 10.1007/s40265-013-0043-1 [doi]
AB  - The armamentarium for the systemic therapy of advanced renal cell carcinoma (RCC) 
      has undergone dramatic changes over the past 6 years. While high-dose interleukin 
      (IL)-2 remains an option for highly selected good and intermediate risk patients 
      with clear-cell histology because of durable complete responses in a small 
      fraction of patients, cytokine-based therapy including interferon (IFN) has been 
      supplanted by vascular-endothelial growth factor (VEGF) and mammalian target of 
      rapamycin (mTOR) inhibitors. Treatment decision is initially based on 
      prognostication of the disease. As metastatic RCC (mRCC) is commonly an indolent 
      disease, a period of observation should always been considered. For good and 
      intermediate risk disease, pazopanib, sunitinib or the combination of bevacizumab 
      plus IFN are considered. Notably, recent data suggest non-inferiority for the 
      efficacy of pazopanib compared to sunitinib coupled with a better toxicity 
      profile. A novel VEGF receptor inhibitor, tivozanib, is expected to be approved 
      based on improvement in PFS when compared to sorafenib in the first-line setting. 
      The use of temsirolimus for poor risk disease is supported by a phase III trial 
      dedicated to this group of patients. The role of cytoreductive nephrectomy in the 
      context of VEGF and mTOR inhibitors is being studied in randomized trials. 
      Selected patients with solitary or oligometastatic disease may be eligible for 
      metastatectomy. Following first-line VEGF inhibitors, second-line therapy with 
      everolimus and axitinib have demonstrated benefits in progression-free survival 
      (PFS). One phase III trial comparing sorafenib and temsirolimus in the 
      post-sunitinib setting showed no difference in PFS, the primary endpoint, but did 
      show a superior overall survival for sorafenib. Sorafenib, pazopanib and axitinib 
      have all demonstrated clinical benefit following cytokines. Therapy following 
      first-line mTOR inhibitors remains undefined, although VEGF inhibitors have 
      demonstrated activity in this setting. Optimal sequencing of agents and 
      individualized therapy based on biomarkers is undergoing investigation. Today, 
      the choice of therapy is based on patient and physician decision, which is a 
      function of comorbidities, toxicity profiles and costs. Clinical trials 
      evaluating novel agents and combinations should be preferred when available since 
      agents in the current therapeutic arsenal have not yielded cures despite 
      extending median survival to greater than 2 years. One noteworthy new class of 
      agents that has yielded durable responses is programmed death (PD)-1 inhibitors, 
      which target a T-lymphocyte checkpoint and are heralding a resurgence of 
      immunotherapy. Finally, optimal therapy for non-clear cell RCC remains to be 
      delineated, although sunitinib, everolimus and other VEGFR-TKI or mTOR inhibitors 
      have all demonstrated modest benefit.
FAU - Escudier, Bernard
AU  - Escudier B
AD  - Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France. 
      escudier@igr.fr
FAU - Albiges, Laurence
AU  - Albiges L
FAU - Sonpavde, Guru
AU  - Sonpavde G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/pathology/surgery
MH  - Clinical Trials as Topic/methods/trends
MH  - Disease Management
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/pathology/surgery
MH  - Neoplasm Metastasis/*drug therapy/pathology
MH  - Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
EDAT- 2013/04/11 06:00
MHDA- 2014/02/04 06:00
CRDT- 2013/04/11 06:00
PHST- 2013/04/11 06:00 [entrez]
PHST- 2013/04/11 06:00 [pubmed]
PHST- 2014/02/04 06:00 [medline]
AID - 10.1007/s40265-013-0043-1 [doi]
PST - ppublish
SO  - Drugs. 2013 Apr;73(5):427-38. doi: 10.1007/s40265-013-0043-1.