部份中文曲贝替定/他比特定处方资料（仅供参考）
商品名称: Yondelis
通用名称: 他比特定注射液
英文名称: trabectedin
汉语拼音: TaBiTeDing Zhusheye
适应症
治疗急性淋巴母细胞白血病、软组织肉瘤和卵巢癌的孤儿药。2007年，EMEA正式批准其用于进展型软组织肉瘤的二线治疗。
对于复发或转移的复杂型软组织肉瘤应用Yondelis(trabectedin)而现治疗优于化疗，而且毒副作用低，有助于保持患者生活质量。对未接受过治疗的、不能切除的、局部晚期或转移性软组织肉瘤患者。
采用Yondelis治疗能获得良好的应答效果，患者病情*进展生存期也明显提高。
用法用量
1.5mg/m2，持续24h静脉滴注,每个月1次,三次一个疗程.　　
不良反应
心电图改变,心动过速,肠梗阻,肺部感染,腹泻,中性细胞减少症,急性肾衰,轻度贫血,咽痛,口疮,恶心呕吐等。
规格
0.25mg/瓶/盒 1mg/瓶/盒
贮藏
避光，2°-8°低温保存
品牌药/生产商：德国Zeltia制药公司研发生产
临床试验：
软组织肉瘤：欧盟研究共入组了266名晚期或转移性脂肪肉瘤与晚期或转移性平滑肌肉瘤患者，这些患者先前均接受过蒽环霉素与异环磷酰胺治疗并且治疗失效。研究对比了两组用药剂量，一组每月给药3次，另一组每3周给药1次。结果显示，每3周给药1次的患者平均无疾病进展期为3.8个月，每月给药3次的患者为2.1个月。
美国研究显示，对于转移性或复发性平滑肌肉瘤或脂肪肉瘤，平均而言，Yondelis治疗组患者的无进展生存期约为4.2个月，相比之下，dacarbazine治疗组患者只有1.5个月的无进展生存期。
卵巢癌：研究共入组了672名治疗后卵巢癌复发或疾病进展的患者，试验对比了脂质体阿霉素单药与Yondelis联合脂质体阿霉素，结果显示Yondelis联合脂质体阿霉素更有效，使用联合疗法的患者无疾病进展期为7.3个月，而使用脂质体阿霉素单药的患者无疾病进展期为5.8个月。
YONDELIS® (trabectedin)
Important Safety Information
CONTRAINDICATIONS - YONDELIS® (trabectedin) is contraindicated in patients with known severe hypersensitivity, including anaphylaxis, to trabectedin.
WARNINGS AND PRECAUTIONS
Neutropenic sepsis, including fatal cases, can occur. In Trial 1, the incidence of Grade 3 or 4 neutropenia, based on laboratory values, was 43% (161/378). Median time to the first occurrence of Grade 3 or 4 neutropenia was 16 days (range: 8 days to 9.7 months). Median time to complete resolution of neutropenia was 13 days (range: 3 days to 2.3 months). Febrile neutropenia (fever ≥38.5°C with Grade 3 or 4 neutropenia) occurred in 18 patients (5%). Ten patients (2.6%) experienced neutropenic sepsis, 5 of whom had febrile neutropenia, which was fatal in 4 patients (1.1%). Assess neutrophil count prior to administration of each dose of YONDELIS® and periodically throughout the treatment cycle. Withhold YONDELIS® for neutrophil counts of less than 1500 cells/microliter on the day of dosing. Permanently reduce the dose of YONDELIS® for life‐threatening or prolonged, severe neutropenia in the preceding cycle.
Rhabdomyolysis - YONDELIS® can cause rhabdomyolysis and musculoskeletal toxicity. In Trial 1, rhabdomyolysis leading to death occurred in 3 (0.8%) of the 378 patients. Elevations in creatine phosphokinase (CPK) occurred in 122 (32%) of the 378 patients receiving YONDELIS®, including Grade 3 or 4 CPK elevation in 24 patients (6%), compared to 15 (9%) of the 172 patients receiving dacarbazine with any CPK elevation, including 1 patient (0.6%) with Grade 3 CPK elevation. Among the 24 patients receiving YONDELIS® with Grade 3 or 4 CPK elevation, renal failure occurred in 11 patients (2.9%); rhabdomyolysis with the complication of renal failure occurred in 4 of these 11 patients (1.1%). Median time to first occurrence of Grade 3 or 4 CPK elevations was 2 months (range: 1 to 11.5 months). Median time to complete resolution was 14 days (range: 5 days to 1 month). Assess CPK levels prior to each administration of YONDELIS®. Withhold YONDELIS® for serum CPK levels more than 2.5 times the upper limit of normal. Permanently discontinue YONDELIS® for rhabdomyolysis.
Hepatotoxicity, including hepatic failure, can occur. Patients with serum bilirubin levels above the upper limit of normal or AST or ALT levels >2.5 x ULN were not enrolled in Trial 1. In Trial 1, the incidence of Grade 3‐4 elevated liver function tests (defined as elevations in ALT, AST, total bilirubin, or alkaline phosphatase) was 35% (134/378). Median time to development of Grade 3‐4 elevation in ALT or AST was 29 days (range: 3 days to 11.5 months). Of the 134 patients with Grade 3 to 4 elevations in LFTs, 114 (85%) experienced complete resolution with the median time to complete resolution of 13 days (range: 4 days to 4.4 months). In Trial 1, the incidence of drug-induced liver injury (defined as concurrent elevation in ALT or AST of more than three times the upper limit of normal, alkaline phosphatase less than two times the upper limit of normal, and total bilirubin at least two times the upper limit of normal) was 1.3% (5/378). ALT or AST elevation greater than eight times the ULN occurred in 18% (67/378) of patients. Assess LFTs prior to each administration of YONDELIS®. Manage elevated LFTs with treatment interruption, dose reduction, or permanent discontinuation based on severity and duration of LFT abnormality.
Cardiomyopathy, including cardiac failure, congestive heart failure, ejection fraction decreased, diastolic dysfunction, or right ventricular dysfunction can occur. In Trial 1, patients with a history of New York Heart Association Class II to IV heart failure or abnormal left ventricular ejection fraction (LVEF) at baseline were ineligible. In Trial 1, cardiomyopathy occurred in 23 patients (6%) receiving YONDELIS® and in four patients (2.3%) receiving dacarbazine. Grade 3 or 4 cardiomyopathy occurred in 15 patients (4%) receiving YONDELIS® and 2 patients (1.2%) receiving dacarbazine; cardiomyopathy leading to death occurred in 1 patient (0.3%) receiving YONDELIS® and in none of the patients receiving dacarbazine. The median time to development of Grade 3 or 4 cardiomyopathy in patients receiving YONDELIS® was 5.3 months (range: 26 days to 15.3 months). Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan before initiation of YONDELIS® and at 2- to 3-month intervals thereafter until YONDELIS® is discontinued. Withhold YONDELIS® for LVEF below lower limit of normal. Permanently discontinue YONDELIS® for symptomatic cardiomyopathy or persistent left ventricular dysfunction that does not recover to lower limit of normal within 3 weeks.
Extravasation Resulting in Tissue Necrosis - Extravasation of YONDELIS®, resulting in tissue necrosis requiring debridement, can occur. Evidence of tissue necrosis can occur more than 1 week after the extravasation. There is no specific antidote for extravasation of YONDELIS®. Administer YONDELIS® through a central venous line.
Embryofetal Toxicity - Based on its mechanism of action, YONDELIS® can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during therapy and for at least 2 months after the last dose of YONDELIS®. Advise males with female partners of reproductive potential to use effective contraception during therapy and for at least 5 months after the last dose of YONDELIS®.
Adverse Reactions - The most common (≥20%) adverse reactions are nausea (75%), fatigue (69%), vomiting (46%), constipation (37%), decreased appetite (37%), diarrhea (35%), peripheral edema (28%), dyspnea (25%), headache (25%).
The most common (≥5%) grades 3‐4 laboratory abnormalities are: neutropenia (43%), increased ALT (31%), thrombocytopenia (21%), anemia (19%), increased AST (17%), and increased creatine phosphokinase (6.4%).
DRUG INTERACTIONS
Effect of Cytochrome CYP3A Inhibitors - Avoid use of strong CYP3A inhibitors (e.g., oral ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, boceprevir, nelfinavir, saquinavir, telaprevir, nefazodone, conivaptan) in patients taking YONDELIS®. Avoid taking grapefruit or grapefruit juice. If a strong CYP3A inhibitor for short‐term use (i.e., less than 14 days) must be used, administer the strong CYP3A inhibitor 1 week after the YONDELIS® infusion, and discontinue it the day prior to the next YONDELIS® infusion.
Effect of Cytochrome CYP3A Inducers - Avoid administering strong CYP3A inducers (e.g., rifampin, phenobarbital, St. John’s wort) to patients who are taking YONDELIS®.