| Abstract: |
The discovery of a relationship for the VHL tumor suppressor gene, hypoxia inducible factor-1 alpha, and vascular endothelial growth factor in the growth of clear-cell renal cell carcinoma (RCC) has identified a pathway for novel targeted therapy. This study evaluated the impact of these agents on metastatic RCC (mRCC), and highlights recent phase II and III trials. A systematic review examined the clinical data for novel targeted agents in mRCC, with a focus on randomized phase II and III trials of the novel targeted agents sunitinib, temsirolimus, sorafenib, and bevacizumab. Several agents, including the small-molecule targeted inhibitors sunitinib, temsirolimus, sorafenib, and the monoclonal antibody bevacizumab, have demonstrated antitumor activity in randomized trials. Superior activity was found with sunitinib and temsirolimus versus cytokines in first-line therapy. Improved progression-free survival was reported with sorafenib and bevacizumab given second-line compared with placebo. Targeted therapies show promising activity in this disease, and they have been changing patient management. Sunitinib and sorafenib were recently approved by the US Food and Drug Administration for treatment of mRCC, These drugs are currently included in clinical practice. © 2006 by American Society of Clinical Oncology. |
| Keywords: |
vasculotropin; cancer survival; genetics; clinical trial; drug activity; fatigue; neutropenia; review; sorafenib; angiogenesis inhibitor; bevacizumab; erlotinib; interferon; sunitinib; cancer risk; diarrhea; drug dose reduction; drug efficacy; hypertension; recommended drug dose; side effect; unspecified side effect; antineoplastic agents; benzenesulfonates; pyridines; skin manifestation; alpha interferon; drug megadose; antineoplastic agent; metabolism; interleukin 2; vasculotropin receptor; metastasis; bortezomib; controlled clinical trial; phase 2 clinical trial; anemia; protein kinase inhibitor; nausea; randomized controlled trial; vomiting; continuous infusion; cetuximab; kidney carcinoma; kidney neoplasms; monoclonal antibody; panitumumab; temsirolimus; lymphocytopenia; rash; protein kinase inhibitors; tumor suppressor gene; cytokine; antibodies, monoclonal; carbonate dehydratase ix; kidney tumor; carcinoma, renal cell; randomized controlled trials; pazopanib; vatalanib; drug derivative; phase 3 clinical trial; axitinib; hormone; indoles; pyrroles; hand foot syndrome; triacylglycerol lipase blood level; angiogenesis inhibitors; alopecia; indole derivative; hypoxia inducible factor 1alpha; everolimus; rapamycin; lapatinib; sirolimus; von hippel lindau protein; pyrrole derivative; benzenesulfonic acid derivative; pyridine derivative; clinical trials, phase ii; clinical trials, phase iii; vhl protein, human; von hippel-lindau tumor suppressor protein
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