Sunitinib
[2] It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006.Imatinib was the first chemotherapeutic agent proven effective for metastatic gastrointestinal stromal tumors and represented a significant development in the treatment of this rare but challenging disease.[5] Sunitinib offers patients with imatinib-resistant gastrointestinal stromal tumors a new treatment option to stop further disease progression and, in some cases, even reverse it.This was shown in a large phase III clinical trial in which patients who failed imatinib therapy (due to primary or secondary resistance or intolerance) were treated in a randomized and blinded fashion with either sunitinib or placebo.[7] In November 2010, Sutent gained approval from the European Commission for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults.[8] In May 2011, the USFDA approved Sunitinib for treating patients with 'progressive neuroendocrine cancerous tumors located in the pancreas that cannot be removed by surgery, or that has spread to other parts of the body (metastatic).Other therapeutic options in this setting are pazopanib (Votrient), sorafenib (Nexavar), temsirolimus (Torisel), interleukin-2 (Proleukin), everolimus (Afinitor), bevacizumab (Avastin), and aldesleukin.Sunitinib also inhibits CD117 (c-KIT),[14] the receptor tyrosine kinase that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors.[2] These include: The fact that sunitinib targets many different receptors, leads to many of its side effects such as the classic hand-foot syndrome, stomatitis, and other dermatologic toxicities.[18] In the placebo-controlled Phase III GIST study, adverse events which occurred more often with sunitinib than placebo included diarrhea, anorexia, skin discoloration, mucositis/stomatitis, asthenia, altered taste, and constipation.[2][5] Serious (grade 3 or 4) adverse events occur in ≤10% of patients and include hypertension, fatigue, asthenia, diarrhea, and chemotherapy-induced acral erythema.[28] Therefore, sunitinib is recommended as a first-line treatment option for people with advanced and/or metastatic renal cell carcinoma who are suitable for immunotherapy and have an ECOG performance status of 0 or 1 (i.e. completely ambulatory).[30] The efficacy of sunitinib is currently being evaluated in a broad range of solid tumors, including breast, lung, thyroid and colorectal cancers.