印度代购科普：什么是膀胱癌？膀胱癌的介绍

据印度代购了解，膀胱癌是指发生在膀胱黏膜上的恶性肿瘤。是泌尿系统最常见的恶性肿瘤，也是全身十大常见肿瘤之一。占我国泌尿生殖系肿瘤发病率的第一位，而在西方其发病率仅次于前列腺癌，居第2位。2012年全国肿瘤登记地区膀胱癌的发病率为6.61/10万，列恶性肿瘤发病率的第9位。膀胱癌可发生于任何年龄，甚至于儿童。其发病率随年龄增长而增加，高发年龄50～70岁。男性膀胱癌发病率为女性的3～4倍。既往将膀胱黏膜上皮称为移行细胞，1998年WHO与国际泌尿病理学会联合建议用尿路上皮一词代替移行细胞一词，以区别于在鼻腔以及卵巢内的移行上皮，使尿路上皮成为尿路系统的专有名词。2004年WHO《泌尿系统及男性生殖器官肿瘤病理学和遗传学》中尿路系统肿瘤组织学分类中膀胱癌的病理类型包括膀胱尿路上皮癌、膀胱鳞状细胞癌、膀胱腺癌，其他罕见的还有膀胱透明细胞癌、膀胱小细胞癌、膀胱类癌。其中最常见的是膀胱尿路上皮癌，约占膀胱癌患者总数的90%以上，通常所说的膀胱癌就是指膀胱尿路上皮癌，既往被称为膀胱移行细胞癌。

Bladder cancer is a malignant tumor that occurs on the bladder mucosa. It is the most common malignant tumor of urinary system and one of the top ten common tumors in the whole body. In China, the incidence of urogenital tumors is the first, and in the west, the incidence is second only to prostate cancer. In 2012, the incidence rate of bladder cancer in China was 6.61 out of 100,000, ranking ninth among malignant tumors. Bladder cancer can occur at any age, even in children. Its incidence increases with age, with the highest incidence between 50 and 70 years old. The incidence of bladder cancer is three to four times higher in men than in women. In 1998, WHO and the International Society of Urology pathology jointly suggested that the term urothelium should be used to replace the term urothelium, so as to distinguish urothelium from urothelium in the nasal cavity and ovary, making urothelium become a proper term for the urinary tract system. The pathological types of bladder cancer included urothelial carcinoma, squamous cell carcinoma of bladder, adenocarcinoma of bladder, and clear cell carcinoma of bladder, small cell carcinoma of bladder, and carcinoid carcinoma of bladder in WHO tumor Pathology and Genetics of Urothelial system and Male Reproductive Organs in 2004. Among them, the most common is bladder urothelial carcinoma, accounting for more than 90% of the total number of bladder cancer patients, usually referred to as bladder urothelial carcinoma, previously known as bladder transitional cell carcinoma.

会发现RET基因融合这种致癌驱动因子，并且在腺癌的亚型，年轻患者和无吸烟史患者中的发生频率更高。在批准高度选择性的RET激酶抑制剂之前，临床试验中已经评估了多靶点激酶抑制剂，例如卡博替尼（Cabozantinib ）和 凡德他尼 (Vandetanib)。但是这些药物的临床疗效很有限。2020年，根据临床试验的总体缓解率和反应持续时间，FDA加速批准了RET抑制剂塞尔帕替尼（Selpercatinib）。

 According to Daigou India, normal RET is a transmembrane receptor belonging to the neurotrophic factor family derived from the glial cell line. Fusion between RET gene and other gene partners results in abnormal expression of fusion gene proteins, resulting in compositional activity, ligand-independent signaling and carcinogenic effects. RET gene fusion is an oncogenic driver found in approximately 1% to 2% of patients with NSCLC, and occurs more frequently in adenocarcinoma subtypes, younger patients, and non-smokers. Prior to the approval of highly selective RET kinase inhibitors, multi-target kinase inhibitors, such as Cabozantinib and Vandetanib, had been evaluated in clinical trials. But the clinical benefits of these drugs are limited. In 2020, the FDA accelerated approval of the RET inhibitor Selpercatinib based on overall response rates and response duration in clinical trials.

　　据印度代购了解，LIBRETTO-001试验对塞尔帕替尼的有效性和安全性进行了研究。LIBRETTO-001是一项在12个国家、65个中心进行的1-2期非盲临床试验，共招募了105名既往接受过中位数为3种系统治疗和39名既往未曾接受治疗的RET融合阳性晚期NSCLC（非小细胞癌）患者。参与试验的患者以28天为一个周期，服用塞尔帕替尼直至疾病发生进展。既往接受以铂类为基础化疗的患者中，88%的患者接受了至少1次剂量的塞尔帕替尼，剂量为160mg,每日2次；既往未曾接受治疗的患者使用塞尔帕替尼的用法用量为每次160mg,每日2次。塞尔帕替尼在既往曾接受以铂类为基础化疗和未曾接受治疗的RET融合阳性NSCLC患者中，均表现出强大的抗肿瘤疗效、颅内抗肿瘤活性和较低的毒性。在既往接受过以铂类为基础化疗的患者中，治疗的客观缓解率为64%(95% CI, 54-73)，而在既往未曾接受治疗的患者中，客观缓解率为85%(95% CI, 70-94)。既往接受铂类为基础化疗患者中位缓解持续时间为17.5个月(95%CI, 55-74)，而未曾接受治疗组未能达到这一水平。

　　据印度代购了解，11例患者在基线调查时，有可测量的肿瘤颅内转移，颅内抗肿瘤治疗的客观缓解率为91% (95% CI, 59-100)，中位缓解持续时间为10.1个月(95% CI, 6.7-NE)。塞尔帕替尼最常见的不良反应(≥25%)包括口干、腹泻、便秘、高血压、疲劳、水肿、皮疹和实验室检查异常，包括转氨酶升高、葡萄糖升高、白细胞减少、白蛋白减少、肌酐增加、血小板减少、总胆固醇增加、钙离子减少和钠离子减少。

According to Daigou India, 11 patients had measurable intracranial tumor metastasis at baseline, the objective response rate of intracranial antitumor therapy was 91% (95% CI, 59-100), and the median response duration was 10.1 months (95% CI, 6.7-NE). Serpa for, the most common adverse reactions (25% or higher) include dry mouth, diarrhea, constipation, high blood pressure, fatigue, swelling, rash and laboratory abnormalities, including transaminase eleations, elevated glucose, white blood cells reduce, albumin and creatinine increased, thrombocytopenia, increased total cholesterol, calcium ion and sodium ion.