|
Trastuzumab (INN; trade names Herclon, Herceptin) is a monoclonal antibody that interferes with the HER2/neu receptor. Its main use is to treat certain breast cancers. The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER protein, Human Epidermal Growth Factor Receptor, binds to Human Epidermal Growth Factor, and stimulates cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.〔 (Jul 5;357(1):39-51. Review /article )〕 A 2014 Cochrane Review examined the safety and efficacy of trastuzumab-containing combination therapies (with chemotherapy, hormone blockers, or lapatinib) for the treatment of metastatic breast cancer. The overall hazard ratios for overall survival and progression free survival were 0.82 and 0.61 respectively. It was difficult to accurately ascertain the true impact of trastuzumab on survival, as in three of the seven trials, over half of the patients in the control arm were allowed to cross over and receive trastuzumab after their cancer began to progress. Thus this analysis likely underestimates the true survival benefit associated with trastuzumab treatment in this population. In these trials, trastuzumab also increased the risk of heart problems, including heart failure (RR 3.49) and left ventricular ejection fraction decline (RR 2.65). In early stage (curable) HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (HR 0.66) and disease-free survival (HR 0.60) relative to comparator arms involving treatment with placebo or chemotherapy. Increased risk of heart failure (RR 5.11) and decline in left ventricular ejection fraction (RR 1.83) were seen in these trials as well. Two trials involving shorter term treatment with trastuzumab did not differ in efficacy from longer trials, but produced less cardiac toxicity. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. The wholesale price is between 1,800.00 and 1,955.00 USD per vial.〔(【引用サイトリンク】url=http://erc.msh.org/dmpguide/resultsdetail.cfm?language=english&code=TRS440I&s_year=2014&year=2014&str=440%20mg&desc=Trastuzumab&pack=new&frm=VIAL&rte=INJ&class_code2=08%2E2%2E&supplement=&class_name=%2808%2E2%2E%29Cytotoxic%20and%20adjuvant%20medicines%3Cbr%3E )〕 ==Medical use== The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months.〔 In early stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within 3 years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%. However, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped. Trastuzumab has had a "major impact in the treatment of HER2-positive metastatic breast cancer". The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone. It is possible to determine the "erbB2 status" of a tumor, which can be used to predict efficacy of treatment with trastuzumab. If it is determined that a tumor is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with trastuzumab. It is surprising that although trastuzumab has great affinity for HER2 and high doses can be administered (due to its low toxicity), 70% of HER2+ patients do not respond to treatment. In fact resistance to the treatment develops rapidly, in virtually all patients. A mechanism of resistance involves failure to downregulate p27 (Kip1) as well as suppressing p27 translocation to the nucleus in breast cancer, enabling cdk2 to induce cell proliferation.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「trastuzumab」の詳細全文を読む スポンサード リンク
|