PMID- 19496716
OWN - NLM
STAT- MEDLINE
DCOM- 20090817
LR  - 20211203
IS  - 1744-8328 (Electronic)
IS  - 1473-7140 (Linking)
VI  - 9
IP  - 6
DP  - 2009 Jun
TI  - Toxicity associated with the long-term use of targeted therapies in patients with 
      advanced renal cell carcinoma.
PG  - 795-805
LID - 10.1586/era.09.29 [doi]
AB  - VEGF and mTOR inhibitors have encouraging clinical activity for patients with 
      advanced renal cell carcinoma (RCC), but may lead to significant short- and 
      long-term toxicities. Although 40-70% of adverse events (AEs) are grade 1 and 2, 
      10-20% of patients develop grade 3 or 4 AEs requiring dose reductions, drug 
      holidays or treatment discontinuation. The long-term impact of the most common 
      grade 3 and 4 AEs observed in Phase III trials evaluating VEGF and mTOR 
      inhibitors, including hypertension, decreased left ventricular ejection fraction, 
      hand-foot-syndrome and myelosuppression, are a concern in RCC patients who are 
      living longer and receiving chronic sequential or combination therapy. There is a 
      clear need to develop a more rational way to individualize therapy for RCC. 
      Long-term follow-up from existing Phase II/III trials should provide us with 
      increased understanding of the potential implications of AEs in RCC patients. 
      Prevention, early recognition and aggressive management of side effects are 
      fundamental to avoid significant long-term complications and unnecessary dose 
      reductions, which can ultimately reduce the efficacy of these novel agents.
FAU - Shepard, Dale R
AU  - Shepard DR
AD  - Department of Solid Tumor Oncology, Cleveland Clinic, Taussig Cancer Institute, 
      9500 Euclid Ave/R35, Cleveland, OH 44195, USA. shepard@ccf.org
FAU - Garcia, Jorge A
AU  - Garcia JA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Expert Rev Anticancer Ther
JT  - Expert review of anticancer therapy
JID - 101123358
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Dose-Response Relationship, Drug
MH  - Drug Delivery Systems
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy
MH  - Protein Kinases/drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors
RF  - 78
EDAT- 2009/06/06 09:00
MHDA- 2009/08/18 09:00
CRDT- 2009/06/06 09:00
PHST- 2009/06/06 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/08/18 09:00 [medline]
AID - 10.1586/era.09.29 [doi]
PST - ppublish
SO  - Expert Rev Anticancer Ther. 2009 Jun;9(6):795-805. doi: 10.1586/era.09.29.