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INTRODUCTION Colorectal cancer is a malignancy of unrestrained cell growth in the colon, rectum, or appendix. Colon cancer affects approximately 1 million people per year and is the third most common cancer worldwide, however it is more common in developed countries due to lifestyle risk factors such as diet. The symptoms of colorectal cancer are highly dependent on the location of the tumor within the bowel and whether it has metastasized. The most common symptoms at presentation include constipation, blood in the stool, weight loss, fever, loss of appetite, nausea, and vomiting, especially in a person over 50. DIAGNOSIS AND TREATMENT OF COLORECTAL CANCER Definitive diagnosis of colorectal cancer is via tumor biopsy, after which CT scans are typically used to determine the extent of the disease. Treatment of colorectal cancer is dependent upon how advanced it is. When caught early, surgery can be greatly effective and curative. However, once metastases are present treatment is often directed more at extending and improving quality of life. According to the American Cancer Society, over 20% of patients present with metastatic colorectal cancer at the time of diagnosis and the 5-year survival rate is less than 60%. Therefore, this deadly disease still proves very difficult to treat after it has progressed past the very early stages. DEVELOPMENT OF REGORAFENIB Researchers have struggled to identify compounds that might prove effective in treating colorectal cancer. In fact, it has been half a decade since the last effective treatment was introduced. Nonetheless, in 2011 a new drug, Regorafenib, emerged from relative obscurity to become a novel therapeutic with unprecedented effectiveness for colorectal cancer. Regorafenib is a multi-targeted tyrosine kinase inhibitor that is currently being investigated in various tumor types. Regorafenib inhibits vascular endothelial growth factor receptor (VEGFR) as well as several other tumor cell signaling kinases including RET, KIT, PDGFR, and Raf, which subsequently inhibits tumor angiogenesis and cell proliferation. The drug was granted orphan drug status by the FDA for use in gastrointestinal stromal tumors (GISTs) in order to fast track its development for use in patients with metastatic, unresectable GISTs, which have progressed despite treatment with imatinib and sunitinib. After the approval of orphan drug status, investigators began to evaluate whether it might be effective in treating other cancers. One of the resulting studies was the CORRECT trial. The CORRECT trial was a multicenter, randomized, double-blind, placebo-controlled study that was carried out internationally with sites in North America, Europe, Australia, China, and Japan. The trial enrolled 760 individuals with metastatic colorectal cancer whose disease had progressed following approved standard treatments and were randomly assigned to either receive regorafenib or placebo. The initial study endpoint was overall survival. However, secondary endpoints included disease control rate, objective tumor response rate, and progression free survival. As of October 2011, the CORRECT trial was halted. The decision to stop the trail came after a significant improvement in overall survival was seen. These findings were the result of a pre-planned interim analysis conducted by an independent Data Monitoring Committee (DMC). As per the recommendation of the DMC the study has now been unblinded, and all patients who were in the placebo group have been offered the drug. Because of these results, regorafenib has been fast-tracked by the FDA for treatment of metastatic colorectal cancer that has progressed after intial treatment. SUMMARY Colorectal cancer is a relatively common malignancy which has remained difficult to treat due to lack of effective chemotherapeutic agents. In 2011, a new tyrosine kinase inhibitor known as regorafenib was shown to increase overall survival in patients with colorectal cancer that had progressed even in the face of heavy treatment. Regorafenib is currently on the fast track through the FDA approval process for treating colorectal cancer as there remains an great, albeit unmet, need in this area. REFERNCES 1. Cunningham, D; Atkin, W, Lenz, HJ, Lynch, HT, Minsky, B, Nordlinger, B, Starling, N (2010 Mar 20). “Colorectal cancer.”. Lancet 375 (9719): 1030-47. 2. Stein, A; Atanackovic, D, Bokemeyer, C (2011 Sep). “Current standards and new trends in the primary treatment of colorectal cancer.”. European journal of cancer (Oxford, England : 1990) 47 Suppl 3: S312-4. 3. S. Hedbom et al. Meeting (2007) ASCO Annual Meeting.Citation: Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. 25(18S):3593 4. Wilhelm SM et al. (2010) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer. 129(1):245-55 RELATED POSTS Three tyrosine kinase inhibitors being used to treat chemo-resistant non-small cell lung carcinoma VEGFR tyrosine kinase inhibitors effective in treating chemo-resistant renal cell carcinoma Related to New tyrosine kinase inhibitor shows unprecedented promise for treatment of colorectal cancer Tyrosine kinase inhibitors are the first effective treatments for gastrointestinal stromal tumors INTRODUCTION Each year 12-14 million people are diagnosed with gastrointestinal stromal tumors (GISTs). The earliest symptom is abdominal discomfort. However, by the time patients seek ... 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