Hui K Gan1, Bostjan Seruga, Jennifer J Knox. 1. Princess Margaret Hospital, Division of Medical Oncology and Hematology, 610 University Avenue, Toronto, Ontario, Canada.
Abstract
BACKGROUND: Until recently, few treatments were available for renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST). Several targeted agents inhibiting key pathogenetic pathways have since been developed for RCC (sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus) and GIST (imatinib, sunitinib). Sunitinib is a multi-kinase inhibitor of VEGFR-2, PDGFR (alpha,beta), FLT-3, KIT, CSF-1 and RET. OBJECTIVE: To summarize the literature regarding the structure, pharmacokinetics, pharmacodynamics, toxicity and current clinical use of sunitinib. Other potential roles for this drug in RCC, GIST and other tumor types will be discussed. METHODS: A literature search identified relevant (pre)clinical studies of sunitinib and other relevant agents. RESULTS/ CONCLUSIONS: Sunitinib revolutionized the management of advanced RCC and GIST. With the realization that cross-resistance between targeted agents is incomplete, evolving strategies include sequential treatment, concurrent treatment, and biomarker development. Sunitinib also shows promise in several other tumor types that lack therapeutic options. What remains less clear is its role in tumors that are not heavily dependent on a central pathogenetic pathway, especially if effective cytotoxic therapies exist. Future clinical trials will clarify whether there is a role for sunitinib in these tumors, possibly in combination with cytotoxic agents.
BACKGROUND: Until recently, few treatments were available for renal cell carcinoma (RCC) and gastrointestinal stromal tumors (GIST). Several targeted agents inhibiting key pathogenetic pathways have since been developed for RCC (sunitinib, sorafenib, bevacizumab, temsirolimus, everolimus) and GIST (imatinib, sunitinib). Sunitinib is a multi-kinase inhibitor of VEGFR-2, PDGFR (alpha,beta), FLT-3, KIT, CSF-1 and RET. OBJECTIVE: To summarize the literature regarding the structure, pharmacokinetics, pharmacodynamics, toxicity and current clinical use of sunitinib. Other potential roles for this drug in RCC, GIST and other tumor types will be discussed. METHODS: A literature search identified relevant (pre)clinical studies of sunitinib and other relevant agents. RESULTS/ CONCLUSIONS:Sunitinib revolutionized the management of advanced RCC and GIST. With the realization that cross-resistance between targeted agents is incomplete, evolving strategies include sequential treatment, concurrent treatment, and biomarker development. Sunitinib also shows promise in several other tumor types that lack therapeutic options. What remains less clear is its role in tumors that are not heavily dependent on a central pathogenetic pathway, especially if effective cytotoxic therapies exist. Future clinical trials will clarify whether there is a role for sunitinib in these tumors, possibly in combination with cytotoxic agents.
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