Sibutramine imatinib (Trametinib) by the United States GlaxoSmithKline (GSK) for treating melanoma drug research and development, is a MEK inhibitor approved by FDA in 2013, trade name: MEKINIST, MEKINIST as a single oral tablet for the treatment with BRAF V600E or V600K mutation of unresectable melanoma or metastatic melanoma in adult patients. The structure of trimetazidine (Trametinib) Figure 1 shows the structure of Trametinib In 2014 the FDA approved MEK inhibitor and BRAF inhibitor imatinib QuMei Dalafeini combination therapy for BRAF V600E or V600K mutation of unresectable or metastatic melanoma. This approval is an open research based on I/II, the results showed that: compared with Dalafeini monotherapy, Sibutramine imatinib and Dalafeini combination therapy can effectively improve the overall response rate (ORR). In May 2013, the two drugs were approved for use as monotherapy, and this is the first approved combination therapy for melanoma. According to reports, 50% patients received single drug BRAF or MEK inhibitor 6-7 months after the initial treatment will produce resistance, therefore, to solve this problem, the need for a more comprehensive MAPK pathway inhibitors, Sibutramine imatinib and Da Rafini is the first approved for the combined treatment of melanoma drugs, provides a reasonable the possibility for the treatment of the disease. In this clinical study, 162 patients with advanced melanoma were treated, and 76% of the patients who had been treated with trimetazidine and Da Rafini had tumor shrinkage or loss, with an average of 10.5 months. The researchers found that, compared with the use of Dalafeini alone in the treatment of patients, 54% patients with tumors to shrink or disappear for an average of 5.6 months. The clinical trial identified whether the combination of trimetazidine and Da Rafini for melanoma could prolong the patient's survival. Research shows that QuMei received imatinib and Dalafeini combined treatment of patients with common adverse reactions include: have a fever, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, and swelling, cough, headache, joint pain, sweating, loss of appetite, constipation and muscle pain. Severe adverse events include bleeding, thrombosis, heart failure, skin and eye problems, and kidney damage. FDA stressed that women of childbearing age should be warned that trimetazidine and Da Rafini could cause birth defects and should be informed that the use of trimetazidine and Da Rafini treatment may lead to infertility. [mechanism of action] Trimetazidine (Trametinib) is a reversible inhibitor of mitogen activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and MEK1 and MEK2 kinase activity. MEK protein is the upstream regulator of the extracellular signal associated kinase (ERK) pathway, which promotes cell proliferation. BRAF V600E mutations cause constitutive activation of the BRAF pathway, including MEK1 and MEK2. Trametinib inhibits the growth of BRAF V600 mutant positive melanoma cells in vitro and in vitro. Trimetazidine (Trametinib) and Da Rafini (dabrafenib) target two different tyrosine kinases in the RAS/RAF/MEK/ERK pathway. The combined use of Trametinib and dabrafenib with either drug alone use lead to BRAF V600 mutation positive melanoma cell lines in vitro greater inhibition and mutation positive melanoma xenograft tumor growth inhibitory effect of V600 extension in BRAF. [indications and uses] Sibutramine imatinib (MEKINIST) is a kinase inhibitor used as monotherapy and in combination with dabrafenib for the approval of a FDA- BRAF and V600K V600E detected mutations in unresectable or metastatic melanoma patients. The use of combination is based on the persistence of reaction rates. Improvements in disease associated symptoms and overall survival associated with MEKINIST and dabrafenib have not been demonstrated. Limitations of use: MEKINIST as monotherapy does not apply to the treatment of patients who have received prior BRAF- inhibitors. [warning and precautions] (1) new primary sexually transmitted diseases, skin and non skin: when MEKINIST is used in combination with dabrafenib, it may occur. The patients were newly monitored before treatment and terminated after treatment and combined treatment. (2) bleeding: a significant bleeding event may occur in patients receiving MEKINIST and dabrafenib. Monitor bleeding signs and symptoms. (3) venous thromboembolism: in combination with MEKINIST and dabrafenib, patients may develop deep vein thrombosis and pulmonary embolism. (4) cardiomyopathy: treatment before, 1 months after treatment, followed, and then assessed LVEF every 2 to 3 months. (5) mice: ophthalmic assessment for any visual impairment. For retinal vein occlusion (RVO), permanent termination of MEKINIST (6) interstitial lung disease (ILD): lung symptoms that are not new or progressive cannot be explained by MEKINIST. For treatment associated ILD and pneumonia, permanent termination of MEKINIST. (7) severe febrile reactions may occur when MEKINIST is used in combination with dabrafenib. (8) severe skin toxicity: monitor skin toxicity and secondary infection. To withstand the 2 grade and 3 grade 4, and despite the interruption of MEKINIST termination of drug rash does not improve within 3 weeks. (9) hyperglycemia: monitoring serum sugar levels in pre-existing diabetes and hyperglycemia patients. (10) fetal fetal toxicity: potentially harmful to the fetus. Adverse reaction (1) the most common adverse reactions of MEKINIST as monotherapy (more than 20%) including skin rash, diarrhea, and lymphedema. (2) MEKINIST dabrafenib combined with the most common adverse reactions (more than 20%) include fever, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache
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