1151 Freeport Road #388
Pittsburgh PA15238
Email: jocelyntanmd@gmail.com
Phone: (412) 301-7472
Fax: (304) 949-8737
Three weeks ago I got word that another new chemotherapy drug has been approved for the treatment of colorectal cancer. Ideal candidates for this drug are patients who failed previous chemotherapy involving one of the following drugs: 5-Fluorouracil, Oxaliplatin, Irinotecan, Cetuximab (also known as Erbitux) and Avastin ( also known as Bevacizumab).This new drug has two active components, trifluridine and tipiracil. Trifluridine is a new nucleoside analog. In other words, a nucleoside is a nitrogen containing biologic compound linked to a sugar, which when phosphorylated, turns into a nucleotide, which is a vital part of the DNA backbone. Trifluridine therefore is a nucleoside analog, meaning it isn't but acts like a nucleoside. It incorporates itself into the DNA structure and interferes with cell growth and proliferation. Tipiracil inhibits the enzyme thymidine phosphorylase, which catalyzes the degradation of Trifluridine, thus allowing it to last longer. Thymidine phosphorylase by itself has pro-angiogenic properties, meaning it promotes blood vessel formation and encourages better blood supply of tumors, so Tipiracil directly stops this advantage. Furthermore, Tipiracil by stopping thymidine phosphorylase, prevents the formation of thymine and 2-deoxy-alpha-D-ribose 1-phosphate. 2DARP is a strong reducing sugar product of thymidine catabolism and causes increased oxidative stress within tumors, promotes release of more tumor blood vessel promoting factors ( angiogenic growth factors) such as interleukin-8, vascular endothelial growth factors VEGF, and matrix metalloproteinase-1 an enzyme which breaks down collagen and extracelular matrix, which is key in promoting tumor metastases. This three mode action of tipiracil ( inhibits thymine production, thymidine phosphorylase VEGF activity, stops ROS and MMP-1 , VEGF and cytokine production)- makes it more attractive since it can potentiate the action of the common colorectal chemotherapy drug 5- fluorouracil whose main action is to inhibit formation of thymine. The RECOURSE trial, a
international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer apparently resulted in statistically significant improvement in overall survival and progression free survival . The drug is given orally, twice a day, for two straight weeks, minus weekends, followed by a two week break. Side effects are listed as anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea,vomiting, abdominal pain,pyrexia. Since it is barely a month since FDA approval ( Sept. 24, 2015) it still has not hit our pharmacy shelves. I am however eager to try this. Will update you again in a few months.
1151 Freeport Road #388
Pittsburgh, PA 15238
Email: ketooncologist@gmail.com
Phone: (412) 301-7472
Fax: (304) 949-8737
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