2010年10月20日，美国食品和药品监督管理局(FDA)已批准赫赛汀(曲妥珠单抗)与化疗联用中(顺铂 [cisplatin]加或卡培他滨[capecitabine]或5-氟尿嘧啶[5-fluorouracil, 5-FU]) 在对其转移疾病既往未曾接受药物的男性和女性.对HER2-阳性转移(癌症已播散)胃或胃食管连接部癌症。 被诊断有转移胃癌的人应有肿瘤用FDA-批准诊断试验确定的HER2状态，因为只有HER2-阳性疾病的人是用赫赛汀加化疗治疗合格者。 执行副主席，产品开发和主要医学官员Hal Barron, M.D说“自从十多年前赫赛汀在HER2-阳性晚期乳癌的批准，我们曾继续研究HER2通路对于其它癌症生长和播散的贡献如何，例如胃癌”“今天赫赛汀与化疗联用的批准为有少数选择选择这个危及生命疾病提供一个重要的新，个体化治疗”。 在2010年1月，欧盟委员会批准赫赛汀与化疗联用为有表现高水平HER2肿瘤有转移胃(胃)癌人们。 关于ToGA研究 The FDA批准是根据阳性结果来自一项国际III期研究，被称为ToGA，显示接受赫赛汀加化疗人们比接受单独化疗活得更长。 ToGA纳入594例有局部晚期或转移，HER2-阳性胃癌的人们，被随机至接受赫赛汀加化疗(顺铂加或卡培他滨或5-FU)或单独化疗，来自最终总生存(OS)分析结果证实赫赛汀加化疗与单独化疗比较OS改善37个百分率(根据HR=0.73。95个百分率CI 0.60-0.91，p=0.0038；中位OS 13.5相比11.0个月)。一项更新的OS分析根据另外一年的随访显示OS改善25个百分率(根据 HR=0.80，95个百分率CI 0.67-0.97，p=0.02；中位OS 13.1相比11.7个月)。 在ToGA中，赫赛汀的安全性谱形与HER2-阳性乳癌和无新或非预期的不良事件研究，所见一致赫赛汀加化疗组中(赫赛汀组1人和单独化疗组2人经受心衰)。赫赛汀加化疗组中5个百分率人，与之比较，单独化疗组中1.1个百分率人有左心室射血分数(LVEF)值低于50个百分率。LVEF从治疗前值绝对减低10个百分率。最常见不良事件是用赫赛汀和化疗与单独化疗比较是增加低白细胞计数(78个百分率)，腹泻(37个百分率)和疲劳(35个百分率)。 在这个试验中，所有人肿瘤都用两种由Dako开发的同伴诊断测试HER2状态。在ToGA中根据HER2筛选结果 (用HER2 IHC和FISH诊断试验二者)，约22个百分率有晚期胃癌人们有HER2-阳性肿瘤。纳入研究要求为任何一种测试HER2过量表达阳性结果。 请参阅赫赛汀部份处方资料 赫赛汀(曲妥珠单抗)静脉输注用 美国最初批准：1998 适应证和用途 转移胃癌剂量和给药方法 适应证和用途 赫赛汀是一种HER2/neu受体拮抗剂适用于； （1）HER2过度表达乳癌的治疗 （2）HER2-过度表达的转移胃或胃食管连接部腺癌是治疗。 剂量和给药方法 只为静脉(IV)输注。不要给予IV推注或大丸给药. HER2-过度表达的乳癌的辅助治疗 给予或: （1）初始剂量4 mg/kg历时90分钟IV输注，然后2 mg/kg历时30分钟IV输注每周共52周，或 （2）初始剂量8 mg/kg历时90分钟IV输注，然后6 mg/kg历时30?90分钟IV输注每三周共52周。 转移HER2-过度表达的乳癌。 初始剂量4 mg/kg历时90分钟IV输注接着随后每周剂量2 mg/kg历时30分钟IV输注。 转移HER2-过度表达的胃癌 初始剂量8 mg/kg历时90分钟IV输注，接着每3周6 mg/kg历时30至90分钟IV输注。 剂型和规格 多次给药小瓶标示含440mg赫赛汀冻干，无菌粉。 禁忌证 无。 警告和注意事项 （1）心肌病 （2）输注反应 （3）化疗-诱发中性粒细胞减少的加重 （4）肺毒性 （5）通过证实有能力的实验室用FDA批准试验进行测试HER2。 （6）胚胎-胎儿毒性 不良事件 乳癌辅助治疗 最常见不良事件(≥ 5%)是头痛，腹泻，恶心，和寒战。 转移乳癌 最常见不良事件(> 10%)是发热，寒战，头痛，感染，充血性心衰，失眠，咳嗽，和皮疹。 转移胃癌 最常见不良事件( ≥10%)是中性粒细胞减少，腹泻，疲劳，贫血，口炎，体重减轻，上呼吸道感染，发热，血小板减少，粘膜炎症，鼻咽炎，和味觉障碍。 在特殊人群中的使用 哺乳母亲：终止哺乳或终止赫赛汀。 【贮藏】 2-8℃下贮存。 本药用配套提供的注射用灭菌水溶解后在2-8℃冰箱中可稳定保存28天。配好的溶液中含防腐剂，因此可多次使用。28天后剩余的溶液应弃去。 如果注射用水中不含防腐剂，则配好的赫赛汀溶液应该马上使用。不要把配的溶液冷冻起来。 含0.9%NaCl的配好的赫赛汀输注液，可在聚氯乙烯或聚乙烯袋中2-8℃条件下稳定保存24小时。30℃条件下，稀释后的赫赛汀液最长可稳定保存24小时。但由于稀释后的赫赛汀不含有效浓度的防腐剂，配制和稀释后溶液最好不是保存在2-8℃冰箱中。从微生物学角度看赫赛汀输注液应马上使用。除非稀释是在严格控制和证实为无菌条件下进行的，否则稀释后的溶液不能保存。 有效期：3年。 Trastuzumab Is Cardiotoxic in Some Elderly Patients With Breast Cancer Older patients with breast cancer who have a history of heart disease and/or diabetes have an increased risk of cardiotoxicity during treatment with trastuzumab, according to Spanish researchers. Cesar Serrano, MD, and colleagues at Vall d’Hebron University Hospital in Barcelona reviewed the records of 45 women aged ≥70 years who had received at least 1 dose of a trastuzumabbased regimen for early or advanced breast cancer and at least 2 left ventricular ejection fraction (LVEF) assessments while on treatment. All patients in the series had undergone treatment since 2005 at the hospital’s breast cancer unit. The study found that 12 (26.7%) women experienced trastuzumab-related cardiotoxicity. Overall, 33% of women with a history of cardiac disease developed trastuzumab-related asymptomatic or symptomatic cardiotoxicity compared with 9.1% of women without a history of cardiac disease (P = .017). Also, 33.3% of diabetic women developed asymptomatic or symptomatic cardiotoxicity versus 6.1% of nondiabetic women (P = .010). Serrano and associates said that the study, to their knowledge, is the first to comprehensively examine trastuzumab-related cardiotoxicity and the cardiovascular risk factors (CRFs) associated with an increased risk in a selected population of elderly patients with breast cancer. The researchers pointed out that trastuzumab is a current standard of care in human epidermal growth factor receptor (HER)-2 positive patients with breast cancer. Cancer incidence increases dramatically with age, and roughly 70% of new cancers are diagnosed in patients aged >65 years. Breast cancer is most common in elderly women. However, clinical trials including patients treated with trastuzumab have been reserved for women aged ≤65 years who have an optimal performance status. Thus, results to date are relevant only for “a relatively young and otherwise healthy patient population” and cannot be necessarily applied to the entire population. Because of trastuzumab’s established benefits and the absence of known predictive risk factors for cardiotoxicity in elderly patients with breast cancer, the investigators decided to determine the agent’s cardiac safety profile in this population of patients in a routine clinical practice setting. In the study, the New York Heart Association classification system was used to document symptomatic cardiotoxicity. Asymptomatic cardiotoxicity was defined as an absolute drop in LVEF ≥10%, resulting in a final LVEF <50% or an absolute drop >20%. Results showed that 3 of 24 (12.5%) patients with early breast cancer and 5 of 21 (23.8%) patients with advanced disease experienced asymptomatic cardiotoxicity. Four women with advanced breast cancer, or 8.9% of the entire study population, developed symptomatic congestive heart failure. All 8 asymptomatic patients with asymptomatic cardiac events had a complete recovery after they stopped taking trastuzumab. The drug was reintroduced in 4 patients, only 1 of whom had a repeat asymptomatic LVEF drop, which improved without treatment withdrawal. The median time to recovery was 6 weeks. Of the 4 patients who developed symptomatic congestive heart failure, 3 recovered their cardiac function at a median of 5 weeks after discontinuing trastuzumab and receiving standard cardiac therapy; 1 patient was able to resume trastuzumab without any additional problems. The fourth patient did not recover cardiac function and had only slight improvement, so her physician decided not to resume any cancer treatment. The patient died 3 months later due to progression of her cancer. While elderly patients with breast cancer who have a history of cardiac disease and diabetes had a significantly increased incidence of cardiac events in this study, other established CRFs, such as high blood pressure and a history of cigarette smoking, did not increase trastuzumab-related cardiotoxicity. Serrano and colleagues said that their findings “can serve to advise clinicians to be aware of symptomatic and asymptomatic cardiac dysfunction in elderly patients, especially in those with 1 or more CRFs.” It is especially important to carefully monitor early symptoms and cardiac function in older patients with breast cancer who are slated for trastuzumab treatment, given that the mortality rate at 5 years after a diagnosis of congestive heart failure is around 50% in patients aged ≥65 years. Physicians should consider referring elderly patients with breast cancer to a cardiologist if 1 or more CRFs are present prior to or during trastuzumab therapy. -------------------------------------------------------------- 提示：以下产品不同规格和不同价格，购买以电话咨询为准！ -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: HERCEPTIN 440mg/Vial 原产地英文药品名: TRASTUZUMAB 中文参考商品译名: 赫赛汀 440毫克/瓶 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克 生产厂家英文名: Genentech -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: HERCEPTIN 440mg/Vial 原产地英文药品名: TRASTUZUMAB 中文参考商品译名: 赫赛汀 440毫克/瓶 中文参考药品译名: 曲妥珠单抗 生产厂家中文参考译名: 基因泰克公司、基因技术公司 生产厂家英文名: Genentech -------------------------------------------------------------- 产地国家: 美国 原产地英文商品名: HERCEPTIN-440mg/Vial, 1Vial 原产地英文药品名: TRASTUZUMAB FOR INJECTION 中文参考商品译名: 赫赛汀-440毫克/瓶，1瓶装 中文参考药品译名: 注射用曲妥珠单抗 生产厂家中文参考译名: 基因泰克 生产厂家英文名: Genentech