奥名润多西他赛-83页PPT精品文档
多西他赛-医肿讲课资料ppt课件
多西他赛新辅助治疗 可手术的乳腺癌
用于可手术乳腺癌的新辅助化疗 －AC→D方案
药 物 ADM CTX DOC 剂量及途径 时间及疗程 d1 q3w×4 60mg/m 2 IV 2 d1 q3w×4 600mg/m IV followed by q3w×4 100mg/m 2 IV(1h) d1
此方案与术前单纯AC方案相比，cCR为 63.6%:40.1% (P<0.001);RR为90.7％:85.5％ (P<0.001),pCR为26.1％:13.7％(P<0.001) 。 术前AC→D各4周期能显著增加cCR和pCR，生存期 结果有待进一步观察。
此方案（TAX306试验）与标准方案AC相比，总有 效率为59％：47％；中位疾病进展时间为37.3月： 31.9月；中位生存时间为22.5月：21.7月。
与AC方案相比，DA方案能显著提高转移性乳腺癌的 肿瘤进展时间和总有效率，但不能显著提高总体生存。
规格
注射液：0.5ml:20mg
1ml:40mg
概
述
通用名：多西他赛注射液 缩 写：DOC 别 名：多烯紫杉醇
作用机制
主要通过与微管蛋白结合，促使微管蛋白聚合并
抑制其解聚，从而抑制细胞的有丝分裂
同紫杉醇相比，多西他赛半衰期更长，能更快地
被肿瘤细胞摄取，在肿瘤细胞内停留的时间更长
臂部，脸部及胸部的局部皮疹，有时伴有搔痒。 皮疹通常可能在滴注多西紫杉醇后一周内发生， 但可在下次滴注前恢复。 严重症状如皮疹后出现脱皮则极少发生。可能 会发生指（趾）甲病变。 可能发生恶心、呕吐或腹泻等胃肠道反应。
其他不良反应
神经毒性
心血管副作用 脱发 无力 粘膜炎 关节痛和肌肉痛 低血压 注射部位反应
多西他赛杂质整理总结文档
多西他赛杂质7（多西他赛EP杂质G）Docetaxel Impurity 7（Docetaxel EP Impurity G）32427D 125354-16-710mg-25mg-50mg-100mg 多西他赛杂质8Docetaxel Impurity 832428D N/A10mg-25mg-50mg-100mg多西他赛杂质9Docetaxel Impurity 932429D N/A10mg-25mg-50mg-100mg多西他赛杂质10Docetaxel Impurity 10324210DN/A10mg-25mg-50mg-100mg多西他赛杂质11Docetaxel Impurity 11324211DN/A10mg-25mg-50mg-100mg多西他赛杂质12Docetaxel Impurity 12324212DN/A10mg-25mg-50mg-100mg多西他赛杂质13（2-苯甲酰-2-戊烯基多西他赛）DocetaxelImpurity 13（2-Debenzoyl-2-pentenoylDocetaxel）324213D 1412898-66-810mg-25mg-50mg-100mg多西他赛杂质14Docetaxel Impurity 14324214DN/A10mg-25mg-50mg-100mgImpurity 15D 250mg-100mg多西他赛杂质16DocetaxelImpurity 16324216DN/A10mg-25mg-50mg-100mg多西他赛杂质17Docetaxel Impurity 17324217D 145533-34-210mg-25mg-50mg-100mg多西他赛杂质18DocetaxelImpurity 18324218D 208406-86-410mg-25mg-50mg-100mg多西他赛杂质19DocetaxelImpurity 19324219DN/A10mg-25mg-50mg-100mg多西他赛杂质20Docetaxel Impurity 20324220D 172018-16-510mg-25mg-50mg-100mg多西他赛杂质21DocetaxelImpurity 21324221D 92950-45-310mg-25mg-50mg-100mg多西他赛杂质22DocetaxelImpurity 22324222D 151636-94-110mg-25mg-50mg-100mgImpurity 23D 150mg-100mg多西他赛杂质24DocetaxelImpurity 24324224DN/A10mg-25mg-50mg-100mg多西他赛杂质25Docetaxel Impurity 25324225D 110258-92-910mg-25mg-50mg-100mg多西他赛杂质26DocetaxelImpurity 26324226D 114915-19-410mg-25mg-50mg-100mg多西他赛杂质27DocetaxelImpurity 27324227DN/A10mg-25mg-50mg-100mg多西他赛杂质28Docetaxel Impurity 28324228DN/A10mg-25mg-50mg-100mg多西他赛杂质29Docetaxel Impurity 29324229DN/A10mg-25mg-50mg-100mg多西他赛杂质30Docetaxel Impurity 30324230DN/A10mg-25mg-50mg-100mgImpurity 31D50mg-100mg多西他赛杂质32Docetaxel Impurity 32324232DN/A10mg-25mg-50mg-100mg多西他赛杂质33Docetaxel Impurity 33324233DN/A10mg-25mg-50mg-100mg多西他赛杂质34Docetaxel Impurity 34324234DN/A10mg-25mg-50mg-100mg多西他赛杂质35Docetaxel Impurity 35324235D 1354900-65-410mg-25mg-50mg-100mg多西他赛杂质36Docetaxel Impurity 36324236D 1095547-98-010mg-25mg-50mg-100mg多西他赛杂质37Docetaxel Impurity 37324237D 1095547-96-810mg-25mg-50mg-100mg多西他赛杂质38Docetaxel Impurity 38324238DN/A10mg-25mg-50mg-100mgImpurity 39D50mg-100mg多西他赛杂质40Docetaxel Impurity 40324240D 133524-69-310mg-25mg-50mg-100mg多西他赛杂质41DocetaxelImpurity 41324241DN/A10mg-25mg-50mg-100mg多西他赛杂质42Docetaxel Impurity 42324242DN/A10mg-25mg-50mg-100mg多西他赛杂质43Docetaxel Impurity 43324243D 154306-81-710mg-25mg-50mg-100mg多西他赛杂质44DocetaxelImpurity 44324244D 147058-27-310mg-25mg-50mg-100mg多西他赛杂质45DocetaxelImpurity 45324245D 154428-10-110mg-25mg-50mg-100mg多西他赛杂质46DocetaxelImpurity 46324246D 157240-36-310mg-25mg-50mg-100mgImpurity 47D 58-250mg-100mg多西他赛杂质48Docetaxel Impurity 48324248D 201856-57-710mg-25mg-50mg-100mg多西他赛杂质49DocetaxelImpurity 49324249D 133577-33-010mg-25mg-50mg-100mg多西他赛杂质50DocetaxelImpurity 50324250DN/A10mg-25mg-50mg-100mg多西他赛杂质51Docetaxel Impurity 51324251D119-52-810mg-25mg-50mg-100mg多西他赛杂质52Docetaxel Impurity 52324252DN/A10mg-25mg-50mg-100mg多西他赛杂质53Docetaxel Impurity 53324253D 165173-47-710mg-25mg-50mg-100mg多西他赛杂质54DocetaxelImpurity 54324254DN/A10mg-25mg-50mg-100mg。
奥名润多西他赛培训课件
5-年生存 率（%） >70 60 50 30 40 10-30
<10
<5
治疗模式
手术 手术或手术+辅助化疗 手术+辅助化疗 手术+辅助化疗
手术+辅助化/ 放疗 或+新辅助化疗（N2 ） 化疗或化疗+放疗
化疗+支持治疗
推荐NSCLC 一线化疗方案
化疗方案 NP TP
GP
DP
药物
长春瑞滨 顺铂
紫杉醇 顺铂 或卡铂
● 成立 南京奥赛康医药集团
国家级荣誉
公司荣誉
公司荣誉
连续五年获得“中国医药研发产品线最佳工业企业”
2010年
2011年
2012年
2013年
2014年
产品概况
全国抗肿瘤药品种最多的企业之一
抗肿瘤类——铂类为主的抗肿瘤产品和抗肿瘤辅助用药产品组合群
全国PPI 针剂品种最全的企业之一
消化类——PPI注射剂产品组群
卫生部《原发性肺癌诊疗规范》2015版
乳腺癌
乳腺癌概况
?全球每年约有 120万妇女患乳腺癌， 50万人死于乳腺癌 ?近10年来，我国的乳腺癌发病率上升了 3.8%，上海、武汉天津、 北京、哈尔滨、等地的发病率都占到当地女性恶性肿瘤的第一、 二位，死亡率为 13.1-8.7/10 万 ? 发病年龄始于 30岁，高峰在 40-49岁 ? 就诊时的病期相对偏晚
其他产品
其他产品
Байду номын сангаас
肿瘤产品群
PPI产品群
铂类主要适应症：
? 头颈部癌，小细胞肺癌，非小细胞肺癌，食管癌等实体瘤 ? 经氟尿嘧啶治疗失败后已转移的结直肠癌
多西他赛(docetaxel)
多西他赛（docetaxel）1概述多西他赛在美国食品药品监督管理局（FDA）相关审评文件中列为窄治疗指数药物（NTIDs）［1］。
依据国内外公开发表的文献资料及相关专业工具书，原研药多西他赛也符合NTIDs的定义及一般特征，其中位有效剂量为18mg/kg，中位致死剂量为30mg/kg，治疗指数（TI）为1.67，属于NTIDs［2-5］。
多西他赛为细胞毒性抗肿瘤药物，1996年获美国FDA批准上市。
多西他赛是我国医保用药，是治疗肺癌、乳腺癌、胃癌、前列腺癌的重要药物之一。
《中国抗癌协会乳腺癌诊治指南与规范（2019年版）》［6］、《中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2020》［7］、《中国晚期乳腺癌规范诊疗指南（2020版）》［8］均推荐多西他赛用于乳腺癌全身治疗。
在国外，美国国家综合癌症网络（NCCN）2020年肿瘤临床实践指南（乳腺癌）［9］、第5版欧洲肿瘤学会（ESO）-欧洲医学肿瘤学会进展期乳腺癌（ABC5）指南［10］、2019年圣加伦（St.Gallen）国际乳腺癌会议指南［11］同样推荐多西他赛用于乳腺癌的全身治疗。
此外，2020年CSCO的各类肿瘤诊疗指南还推荐多西他赛用于非小细胞肺癌［12］、胃癌［13］和前列腺癌［14］的全身治疗。
2安全用药提示2.1替换使用多西他赛的仿制替代带来皮肤毒性风险增加：Yang 等［15］开展的回顾性研究提示，替换原研多西他赛带来皮肤毒性发生率增加。
此外，由于仿制替换可能带来的疗效降低或不良反应增加，可能导致患者的住院时间延长，使患者需要接受额外的医疗项目以改善症状，最终导致患者的综合医疗支出增加，也导致其医保负担加重。
Poirier等［16］开展的一项研究提示，接受仿制多西他赛治疗的患者，中性粒细胞减少性发热的发生率显著高于原研组，部分患者因此需要使用更多粒细胞-集落刺激因子（G-CSF）治疗，因而治疗费用增加；而部分患者可能因此而停药，患者生存等临床疗效指标受到影响。
抗肿瘤药物规范化配置和合理使用ppt课件
溶媒为NS或 5%GS
紫杉醇 卡铂水剂：伯尔定 拓扑替康：金喜素
和美新 多西他赛：艾素、希存
泰索帝、奥名润
美罗华
5-Fu 卡莫司汀
合理使用
1、最适药物和剂量 2、最佳溶酶选择 3、最适配置浓度和滴速 4、配置后的稳定性 5、给药顺序 6、给药时间 7、毒副作用
规范的医嘱设计 药师医嘱审核
最适配置浓度和滴速
引发紫杉醇的剂量限制性毒性
先用紫杉醇 再用顺铂
依托泊苷与顺铂
依托泊苷的作用靶点是DNA拓扑异构 酶Ⅱ，抑制有丝分裂，使细胞分裂 停止于S期或G2期，属于细胞周期特 异性药物
顺铂属于细胞周期非特异性药物
先用依托泊苷 后用顺铂
合理使用
1、最适药物和剂量 2、最佳溶酶选择 3、最适配置浓度和滴速 4、配置后的稳定性 5、给药顺序 6、给药时间 7、毒副作用
总结
一、概论、规范化的配置及注意事项
二、合理使用和注意事项
1、最适药物和剂量 2、最佳溶酶选择 3、最适配置浓度和滴速
规范的医嘱设计 药师医嘱审核
4、配置后的稳定性
5、合适的给药顺序
6、合适的给药时间
7、毒副反应
请记住
没有安全的药物 只有安全的医师、药师、护士 合理的处方 合理的配置 合理的给予
溶媒及液体量 5%GS 500ml
浓度
滴注速度 小于 6 小时
紫杉醇脂质体 （力扑素）
5%GS 250-500ml
3 小时
ቤተ መጻሕፍቲ ባይዱ
多柔比星脂质体 (楷莱) 奥沙利铂 (乐沙定)
吡柔比星
卡铂粉剂
5%GS 250ml
5%GS 250-500ml 〉0.2 mg/ml 5%GS 或 注射用水
【优秀资料】多西他赛首次应用的注意事项及过敏反应的处理PPT
优选多西他赛首次应用的注意事项及过敏 反应的处理
紫杉醇类药物
紫杉醇 多西他赛 紫杉醇脂质体 白蛋白结合型紫杉醇
紫杉醇来源于美国西部紫杉树皮中分离得到 多西紫杉醇来源于欧洲针叶为原料的半合成品
适应症
1.适用于局部晚期或转移性乳腺癌的治疗。 2.适用于局部晚期或转移性非小细胞肺癌的治疗，即使是 在以顺铂为主的化疗失后。 3.联合曲妥珠单抗，用于HER-2基因过度表达的转移性乳 腺癌患者的治疗。
所有病人在接受多西他赛治疗期前均必须 口服糖皮质激素激素化，如地塞米松，在 多西他赛滴注一天前服用，每天16mg， 持续至少3天(或前一天夜晚地塞米松20mg ivgtt)，以预防过敏反应和体液潴留。
多西他赛滴注当天应用地塞米松、苯海拉 明等预防过敏。
过敏反应处理
只有潮红或局部皮肤反应的症状不必中断 治疗
严重过敏反应
较为少见，一旦出现若未及时抢救，往往 可以致死。 常表现为多西他赛输入后很快有低血压和 支气管痉挛为主要表现的过敏反应出现
严重过敏反应处理
急救处理 立即停止输液，更换输液器及液 体，千万不要马上拔出输液针头。因为病人 如果发生过敏性休克时，血压降低，静脉萎 陷，导致穿刺困难。平卧，保持呼吸道通常， 立即给予5L/min鼻导管吸氧，地塞米松 10mg静脉推注，异丙秦25mg肌肉注射， 林格液500mL扩容和心电监测，备好急救 器材进行对症
用法用量
用量：推荐剂量为75mg/m2滴注1h，每3周1 次。
用法用量
临用前将多西他赛所对应的溶剂全部吸入 对应的溶液中，轻轻振摇混合均匀，将混 合后的药瓶室温放置5分钟，然后检查溶液 是否均匀澄明，根据计算病人所用药量， 用注射器吸入混合液，注入5％葡萄糖注射 液或0.9％氯化钠注射液的注射瓶或注射袋 中，轻轻摇动，混合均匀，最终浓度不超 过0.9mg/ml。
多西他赛 帕妥珠单抗
CLINICAL TRIALPhase II,multicenter,open-label,randomized study of YM155plus docetaxel as first-line treatment in patients with HER2-negative metastatic breast cancerMichael R.Clemens •Oleg A.Gladkov •Elaina Gartner •Vladimir Vladimirov •John Crown •Joyce Steinberg •Fei Jie •Anne KeatingReceived:8December 2014/Accepted:8December 2014/Published online:30December 2014ÓThe Author(s)2014.This article is published with open access at Abstract The objective of this study was to assess the efficacy and tolerability of YM155,a survivin suppressor,in combination with docetaxel,compared with docetaxel alone in patients with HER2-negative metastatic breast cancer.This phase II,multicenter,open-label,2-arm study randomized patients (C 18years)with histologically or cytologically confirmed stage IV HER2-negative meta-static breast cancer and C 1measurable lesion,to receive docetaxel alone or docetaxel plus YM155.The primary endpoint was progression-free survival (PFS).Secondary endpoints included objective response rate (ORR),overall survival (OS),duration of response (DOR),clinical benefit rate (CBR),time to response (TTR),biomarker assessment,and analysis of circulating tumor cells.Patients were women diagnosed with HER2-negative breast cancer;mosthad received prior drug therapies.The median PFS was 8.4months with YM155plus docetaxel (n =50)and 10.5months with docetaxel alone (n =51;HR 1.53;95%CI 0.83,2.83;P =0.176).No statistically significant dif-ferences were observed for secondary endpoints,although slightly greater OS (630vs 601days;P =0.768),CBR (84.3vs 82.0%;P =0.855),DOR,and TTR were observed with docetaxel alone compared with YM155plus docetaxel,whereas ORR was similar (25.5vs 26.0).The most common TEAEs observed with YM155plus doce-taxel compared with docetaxel alone were neutropenia (83.3vs 84.3%),alopecia (62.5vs 52.9%),fatigue (50vs 41.2%),and nausea (37.5vs 41.2%).Although YM155is a novel drug that suppresses survivin,YM155plus doce-taxel exhibited no statistically significant differences in endpoints compared with docetaxel alone.The combina-tion regimen was well tolerated.Keywords YM155ÁSurvivin ÁHER2ÁMetastatic breastcancerIntroductionBreast cancer is the most common potentially fatal form of cancer in women and is the leading cause of death from cancer in women worldwide [1].It is estimated that there will be approximately 235,000new cases of invasive breast cancer and more than 40,000breast cancer deaths in the United States in 2014[2].The majority of patients will be diagnosed with early stage disease [3],which is amenable to curative treatment with surgical care and/or radiation [4];however,6–10%of patients will present with meta-static breast cancer [5],and up to 30%of all patients may ultimately develop metastatic disease [6].M.R.Clemens (&)Innere Medizin I,Klinikum Mutterhaus de Borromaerinnen GmbH,Trier,Germanye-mail:Clemens@mutterhaus.deO.A.GladkovChelyabinsk Regional Clinical Oncology Dispensary,Chelyabinsk,RussiaE.GartnerBarbara Ann Karmanos Cancer Institute,Wayne State University,Detroit,MI,USAV.VladimirovPyatigorsk Oncology Dispensary,Pyatigorsk,RussiaJ.CrownIreland Cooperative Oncology Research Group,Dublin,Ireland J.Steinberg ÁF.Jie ÁA.KeatingAstellas Pharma Global Development,Northbrook,IL,USABreast Cancer Res Treat (2015)149:171–179DOI 10.1007/s10549-014-3238-6While metastatic breast cancer generally is incurable, systemic therapy can provide meaningful prolongation of survival and palliation of the distressing symptoms of cancer[7,8].The choice of systemic therapy is increas-ingly determined by biological markers predictive of response to targeted therapy.Patients with hormone receptor positive disease will frequently benefit from endocrine therapies[9].When the nearly inevitable development of resistance to endocrine therapy occurs [10],these patients can still derive benefit from cytotoxic chemotherapy[11].Patients whose cancer has an alteration (usually an amplification)of the HER2gene derive sub-stantial benefit from anti-HER2therapeutics such as trast-uzumab given in combination with chemotherapy or endocrine therapy[12].Approximately15%of patients have tumors that do not express the estrogen or progesterone receptors,and do not have altered HER-2[9].There are currently no markers predictive of response for patients with these‘‘triple neg-ative’’tumors,and conventional cytotoxic chemotherapy remains the standard of care[11].Unfortunately,prognosis remains poor due to high rates of relapse and chemore-sistance in this subset of breast cancer patients[13].New molecularly targeted systemic therapies for triple negative breast cancers(TNBC)are urgently needed.One such candidate target molecule is survivin,a member of the‘‘inhibitor of apoptosis protein’’family that contributes to increased proliferation and resistance to apoptosis in tumor cells[14].Overexpression of survivin has been demonstrated in metastatic breast cancer com-pared with normal breast tissue[15].A recent meta-ana-lysis found that increased expression of survivin was significantly associated with unfavorable overall survival (OS)in patients with breast cancer[16].YM155is a small molecular suppressor of survivin. Continuous infusion of YM155significantly reduced tumor size and the incidence of spontaneous metastasis,as well as prolonged survival,in a mouse model of metastatic TNBC [17].In vitro studies demonstrated that inhibition of apoptosis by survivin required interaction with microtu-bules[18],providing a powerful rationale for the study of survivin together with anti-microtubule agents such as taxanes.YM155in combination with the microtubule-tar-geted agent docetaxel induced greater apoptosis compared with either agent alone,resulting in complete tumor regression in a mouse TNBC xenograft model[19].The results of a phase I study indicated that YM155was well tolerated with manageable toxicities in patients with advanced solid tumors,including breast cancer,that were refractory to standard therapy[20].Additionally,findings from an open-label,single-arm,single-center study of YM155plus docetaxel in patients with advanced hormone refractory prostate cancer and other tumors showed responses in a few patients with breast cancer,supporting the design and execution of the present study[21].The objective of the current phase II study was to assess the effects of YM155in combination with docetaxel compared with docetaxel alone on progression-free sur-vival(PFS)in patients with HER2-negative metastatic breast cancer.MethodsStudy designThis was a phase II,multicenter,open-label,randomized, 2-arm study(NCT01038804)conducted in the United States,Europe,and Russia.Local institutional review boards and independent ethics committees,or both, approved the study protocol and informed consent forms before use.The study was conducted in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice,the European Clinical Trial Directive,and applicable laws and regulations.Each patient provided written informed consent before study enrollment.Study populationInclusion criteriaPatients aged C18years with histologically or cytologi-cally confirmed stage IV HER2-negative metastatic breast cancer and C1measurable lesion(RECIST criteria,version 1.1)were eligible for enrollment.HER2-negative breast cancer was defined as negativefluorescence in situ hybridization(FISH),0or1?immunohistochemistry (IHC),or IHC2?with negative FISH.Patients had an Eastern Cooperative Oncology Group performance status B1at baseline.In general,priorfirst-line chemotherapy for metastatic breast cancer was not permitted.However,prior cytotoxic therapy was permitted if it was administered in the neoadjuvant or adjuvant setting C3weeks before baseline.Patients with prior docetaxel treatment were eli-gible if they had no evidence of recurrent disease within 12months of completing treatment.Prior treatment with a kinase inhibitor or hormonal therapy also was permitted if administered C4and C2weeks,respectively,before baseline,and prior palliative radiation therapy was allowed if completed C2weeks before baseline.For a brief period, the protocol was amended to enroll patients who had pre-viously receivedfirst-line chemotherapy,but this was revised back to the original criteria of no prior therapy for metastatic disease based upon preclinical data that sug-gested that YM155was a p-glycoprotein substrate.Exclusion criteriaPatients were excluded if they had hypersensitivity to docetaxel or polysorbate80;major surgery,open biopsy,or significant traumatic injury within28days before baseline or anticipated need for major surgery during the study; neuropathy grade C2at baseline;inadequate marrow at baseline;inadequate hepatic function and renal function,or both,at baseline;known brain or leptomeningeal metastasis; known immunodeficiency virus,hepatitis B surface antigen, or hepatitis C antibody;or significant and/or uncon-trolled cardiac,renal,hepatic,or other systemic disorders or significant psychological conditions at baseline.Treatment regimenOne cycle was considered21days and was divided into a 7-day treatment period followed by a14-day(Arm A; YM155plus docetaxel)or a20-day(Arm B;docetaxel alone)observation period.YM155was administered by continuous infusion at a dose of5mg/m2/day for168h.The YM155infusion was initiated on day1within1h of com-pletion of docetaxel dosing using a portable infusion pump to administer study drug through a dedicated central line, port,or peripherally inserted central catheter.Dose reduction of YM155to3.6mg/m2/day was permitted at the investi-gator’s discretion in patients with a grade3or4adverse event(AE),with the exception of weight loss or gain, anorexia,alopecia,and fatigue.Infusion of YM155and docetaxel was interrupted until the AE resolved to grade B1 or returned to baseline,and infusion of YM155could then be restarted at the original dose of5mg/m2/day or reduced to3.6mg/m2/day at the discretion of the investigator.Docetaxel[22]was administered by intravenous infusion for1h on day1every21-day cycle at a dose of75mg/m2in patients treated with YM155plus docetaxel and75or 100mg/m2in patients treated with docetaxel alone at the discretion of the investigator.Dose reduction of docetaxel to 75mg/m2was permitted at the discretion of the investigator in patients with febrile neutropenia or an absolute neutrophil count\500cells/mm3lasting[1week and in patients with severe or cumulative cutaneous reactions.In the event that these AEs were ongoing,further dose reduction of docetaxel to55mg/m2or discontinuation of docetaxel was permitted at the discretion of the investigator.In patients with a grade 3or4AE,with the exception of peripheral neuropathy, weight loss or gain,anorexia,alopecia,and fatigue,doce-taxel treatment was interrupted until the AE resolved to grade B1or returned to baseline and then could be restarted at75for patients receiving100mg or55mg/m2for patients receiving75mg/m2at the time of the AE.Discontinuation of docetaxel treatment was required in patients with grade3 or4neuropathy.Retreatment criteriaThe following criteria must have been met before a patient began the next cycle of treatment:no evidence of disease progression based on radiological and/or clinical assess-ments,and any YM155-and/or docetaxel-related toxicity must have either resolved to a grade of B1or returned to baseline level.AssessmentsThe primary efficacy endpoint was PFS.Subgroup analyses of PFS were performed according to TNBC or hormone receptor positive status.The secondary efficacy endpoints assessed included objective response rate(ORR),OS,dura-tion of response(DOR),clinical benefit rate(CBR),and time to response(TTR).Patients were evaluated by computed tomography,magnetic resonance imaging,or both,every 6weeks(cycle1and2)within5days of the initial docetaxel infusion and every12weeks thereafter.Objective tumor assessments were determined using RECIST,version1.1.Blood samples were collected from all patients during screening and cycles1–3to assess biomarkers,including caspase-cleaved cytokeratin18(M30ApoptosenseÒELISA,PEVIVA AB,Broma,Sweden),a tumor apoptosis marker.Blood samples were collected during cycles1and 2for analysis of circulating tumor cells.Safety and tolerability assessments included AEs and clinical laboratory evaluations.Statistical analysesThe efficacy analyses were conducted on the full analysis set(FAS)and per protocol(PP)set.The FAS included all patients randomized into the study and was considered the primary analysis set.The PP set included all randomized patients who were administered C1dose of their assigned study regimen,had histologically or cytologically proven adenocarcinoma of the breast that was HER2-negative,had no known brain or leptomeningeal metastasis,had no his-tory of other malignancy within5years before thefirst dose of YM155,except for treated basal or squamous cell carcinoma of the skin or in situ cervical cancer,and did not have major protocol deviations.Demographic data and baseline disease and treatment characteristics were summarized using descriptive statis-tics.The median PFS,including subgroup analyses of PFS, OS,and DOR were estimated using the Kaplan–Meier method reported with corresponding95%CI.PFS and OS were analyzed between treatment arms using a two-sided log-rank test stratified by prior taxane therapy and triple negative status(a=0.05).PFS also was comparedbetween treatment arms using the hazard ratio,corre-sponding95%CI,and P value from the stratified Cox proportional hazards regression model.ORR and CBR were compared between treatment arms using the stratified Cochran-Mantel-Haenszel test,and the difference in response rates and corresponding95%CIs were estimated using large sample methods and unpooled variance esti-mates.The TTR was summarized using descriptive statistics.Approximately100patients(randomized in a1:1ratio) stratified by prior taxane therapy and triple negative status (yes or no for both)were required to observe67PFS events (progressive disease or death).The sample size had55% power to detect a true hazard ratio of0.60(median PFS of 10vs6months).Safety was assessed in all patients who received C1 dose of study regimen and summarized using descriptive statistics or frequency distributions,as appropriate. ResultsBaseline demographics and characteristicsOf119patients screened,101were enrolled and random-ized to treatment and99received the drug.At baseline,all patients were women diagnosed with HER2-negative metastatic breast cancer,and the majority had received prior drug therapies,principally in the adjuvant or neoad-juvant setting(Table1).Table1Baseline characteristics(full analysis set)NOS not otherwise specifieda HER2,estrogen,and progesterone receptors Characteristic YM155?docetaxel(n=50)Docetaxel(n=51)Total(N=101) Sex,n(%)Female50(100)51(100)101(100) Median age,years(range)57.0(34–79)55.0(25–77)55.0(25–79) Race,n(%)White47(94.0)48(94.1)95(94.1) Black or African American1(2.0)1(2.0)2(2.0) Asian1(2.0)01(1.0) Other1(2.0)2(3.9)3(3.0) Subtype at diagnosis,n(%)Ductal37(74.0)33(64.7)70(69.3) Lobular4(8.0)8(15.7)12(11.9) Paget’s disease and infiltrating2(4.0)02(2.0) Medullary,NOS01(2.0)1(1.0) Papillary01(2.0)1(1.0) Other7(14.0)8(15.7)15(14.9) Tumor grade,n(%)Grade11(2.0)2(3.9)3(3.0) Grade224(48.0)19(37.3)43(42.6) Grade315(30.0)16(31.4)31(30.7) Unknown10(20.0)14(27.5)24(23.8) Tumor receptor status,n(%)Triple receptor negative a13(26.0)12(23.5)25(24.8) Estrogen receptor statusPositive34(68.0)35(68.6)69(68.3) Negative13(26.0)14(27.5)27(26.7) Unknown3(6.0)2(3.9)5(5.0) Progesterone receptor statusPositive22(44.0)33(64.7)55(54.5) Negative23(46.0)14(27.5)37(36.6) Unknown5(10.0)4(7.8)9(8.9) Prior drug therapy,n(%)43(86.0)44(86.3)87(86.1) Prior taxane therapy,n(%)11(22.0)9(17.6)20(19.8)Treatment exposurePatients in the YM155plus docetaxel group completed a median of6.0cycles of YM155infusion;4(8.3%)patients experienced YM155dose reduction,and8(16.7%)patients experienced an interruption.In addition,patients in this arm received a median of6.0cycles and a cumulative total dose of679.0mg of docetaxel infusion;9(18.8%)patients experienced a dose reduction and no patients an interruption.Patients in the docetaxel arm completed a median of 7.43cycles and received a median cumulative total dose of 827.5mg of docetaxel infusion;12(23.5%)patients experienced a dose reduction and no patients experienced an interruption.Primary and secondary endpointsThe median PFS was8.4months in patients treated with YM155plus docetaxel compared with10.5months in patients administered docetaxel alone.This difference was not statistically significant(P=0.172;Table2).Kaplan–Meier plots of PFS are presented in Fig.1a.The docetaxelTable2Analysis of primary and secondary efficacy endpoints for the full analysis populationCBR clinical benefit rate,DOR duration of response,FAS full analysis set,NA not available, ORR objective response rate,OS overall survival,PFS progression-free survival*At the time of data cutoff, median DOR had not been reached Clinical outcome YM155?Docetaxel(FAS,n=50)Docetaxel(FAS,n=51)P valueFASPrimary efficacy endpointMedian(95%CI)PFS,days251.0(172,333)315.0(202,433)0.172 HR(95%CI) 1.53(0.83,2.83)0.176 Secondary efficacy endpointsORR,n(%)13(26.0)13(25.5)0.987 CBR,n(%)41(82.0)43(84.3)0.855 Median OS,days601.0630.00.768 Median DOR,days231.5NA*NAarm demonstrated slightly better secondary endpoints com-pared with the YM155plus docetaxel arm,but no statisti-cally significant differences between the treatment arms were observed (Table 2;Fig.1b–d).In addition,median PFS,OS,and DOR values were similar between the FAS and PP populations,with no significant differences between treatment arms for the PP population (data not shown).Biomarker analyses for the presence of caspase-cleaved cytokeratin 18,a specific marker for epithelial cell apop-tosis,suggested a slightly higher percentage of tumor apoptosis with YM155plus docetaxel (31.4%)compared with docetaxel alone (18.3%).Circulating tumor cells were very low and no differences could be shown betweenTable 3Treatment-emergent adverse events occurring in C 10%in either treatment arm (safety analysis population)Parameter,n (%)YM155?docetaxel (n =48)Docetaxel (n =51)Hematologic Neutropenia 40(83.3)43(84.3)Leukopenia 13(27.1)17(33.3)Anemia13(27.1)6(11.8)Febrile neutropenia 11(22.9)5(9.8)Lymphopenia 3(6.3)6(11.8)Nonhematologic Alopecia 30(62.5)27(52.9)Fatigue 24(50.0)21(41.2)Nausea 18(37.5)21(41.2)Dyspnea 16(33.3)7(13.7)Diarrhea 11(22.9)10(19.6)Edema peripheral 9(18.8)12(23.5)Neuropathy peripheral 7(14.6)12(23.5)Stomatitis 11(22.9)8(15.7)Decreased appetite 8(16.7)9(17.6)Asthenia 7(14.6)8(15.7)Constipation 6(12.5)8(15.7)Cough 6(12.5)8(15.7)Dysgeusia 5(10.4)9(17.6)Headache8(16.7)5(9.8)Mucosal inflammation 8(16.7)5(9.8)Pyrexia 8(16.7)5(9.8)Arthralgia 8(16.7)4(7.9)Back pain 9(18.8)2(3.9)Bone pain 4(8.3)7(13.7)Nail disorder 6(12.5)5(9.8)Urinary tract infection 6(12.5)5(9.8)Pain in extremity 4(8.3)6(11.8)Insomnia6(12.5)3(5.9)Peripheral sensory neuropathy 3(6.3)6(11.8)Myalgia2(4.2)6(11.8)Oropharyngeal pain5(10.4)Table 4Treatment-emergent grade C 3adverse events (safety ana-lysis population)Parameter,n (%)YM155?Docetaxel (n =48)Docetaxel (n =51)Grade 3Neutropenia 19(39.6)12(23.5)Leukopenia6(12.5)8(15.7)Febrile neutropenia 8(16.7)4(7.8)Lymphophenia 3(6.3)4(7.8)Dyspnea 3(6.3)1(2.0)Pneumonia2(4.2)2(3.9)Central line infection 2(4.2)1(2.0)Palmar-plantarerythrodysasthesia syndrome 1(2.1)2(3.9)Deep vein thrombosis 2(4.2)0Pleural effusion 2(4.2)0Increased alanine aminotransferase 02(3.9)Peripheal neuropathy 02(3.9)Anemia 1(2.1)1(2.0)Asthenia 1(2.1)1(2.0)Atrial fibrillation 1(2.1)1(2.0)Bone pain1(2.1)1(2.0)Catheter-related infection 1(2.1)1(2.0)Cellulitis 1(2.1)1(2.0)Dehydration1(2.1)1(2.0)Decreased white blood cell count 1(2.1)1(2.0)Syncope 1(2.1)1(2.0)Atrial thrombosis 1(2.1)0Clostridium difficile colitis 1(2.1)0Decreased appetite 1(2.1)0Diarrhea1(2.1)0Electrocardiogram T wave inversion 1(2.1)0Excoriation 1(2.1)0Hypoalbuminemia 1(2.1)0Hypotension 1(2.1)0Increased gamma-glutamyltransferase 1(2.1)0Mucosal inflammation 1(2.1)0Nail disorder 1(2.1)0Pericarditis 1(2.1)0Platelet disorder 1(2.1)0Polyneuropathy 1(2.1)0Pulmonary embolism 1(2.1)0Respiratory failure 1(2.1)0Stomatitis1(2.1)0Superior vena cava occlusion 1(2.1)0Thrombosis1(2.1)0Vascular access complication 1(2.1)0Back pain1(2.0)the two treatment arms.However,for both analyses,the sample sizes were very small and no statistical correlations could be made.Safety and tolerabilityAll patients in the safety analysis population(n=99) experienced C1TEAE(Table3).The most common TE-AEs in both treatment groups were neutropenia,alopecia, fatigue,and nausea.Most TEAEs were grade3or4,and the events reported in the YM155plus docetaxel arm were judged more often to be possibly or probably related to study drug,whereas none of the events in the docetaxel alone arm were judged to be possibly or probably related (Tables3,4).The most common drug-related TEAEs in the YM155 plus docetaxel arm were neutropenia(n=18[37.5%]), fatigue(n=13[27.1%]),and febrile neutropenia(n=9 [18.8%]).A total of14(29.2%)patients administered YM155plus docetaxel and9(17.6%)patients adminis-tered docetaxel alone experienced a TEAE leading to study discontinuation.TEAEs leading to study discontinuation that occurred in C2patients in a treatment arm were febrile neutropenia and leukopenia(each n=2[4.2%])in patients administered YM155plus docetaxel andfluid retention,palmar-plantar erythrodysesthesia syndrome,and peripheral neuropathy(each n=2[3.9%])in patients administered docetaxel alone.Serious AEs(SAEs)were experienced by25(52.1%) patients administered YM155plus docetaxel and17 (33.3%)administered docetaxel alone(Table5).SAEs that occurred in C5%of patients in either treatment group included febrile neutropenia,neutropenia,and pneumonia (Table5).A total of56(56.6%)patients died during the study;28(58.3%)patients were treated with YM155plus docetaxel and28(54.9%)patients received docetaxel alone. Most of the deaths(87.5%)were attributed to breast cancer. In patients administered YM155plus docetaxel,two deaths were attributed to hepatic failure,one to a cerebrovascular accident,one to general state degradation,and the cause of death in one patient was unknown.In patients who received docetaxel alone,one death was attributed to sepsis;in oneTable4continuedParameter,n(%)YM155?Docetaxel(n=48)Docetaxel (n=51)Bronchitis01(2.0) Catheter site infection01(2.0) Cerebral infarction01(2.0) Decreased neutrophil count01(2.0) Fatigue01(2.0) Fluid retention01(2.0) Herpes zoster01(2.0) Hydronephrosis01(2.0) Hyponatremia01(2.0) Hypophosphatemia01(2.0) Increased blood glucose01(2.0) Infective arthritis01(2.0) Neck pain01(2.0) Pain in extremity01(2.0) Paresthesia01(2.0) Pelvic pain01(2.0) Peripheral edema01(2.0) Pleurisy01(2.0) Pyrexia01(2.0) Rash01(2.0) Wound infection01(2.0) Grade4Neutropenia21(43.8)30(58.8) Leukopenia5(10.4)4(7.8) Febrile neutropenia2(4.2)1(2.0) Decreased neutrophil count1(2.1)1(2.0) Decreased white blood cellcount1(2.1)1(2.0) Pulmonary embolism1(2.1)1(2.0) Catheter sepsis1(2.1)0 Fatigue1(2.1)0 Increased blood creatinine1(2.1)0 Infection1(2.1)0 Metastases to central nervoussystem01(2.0) Sepsis1(2.1)0 Septic shock1(2.1)0 Thoracic vertebral fracture1(2.1)0 Grade5Breast cancer1(2.1)0 Cerebrovascular accident1(2.1)0Table5Most common serious adverse events regardless of causality occurring in C5%of patients(safety analysis population)SAE,n(%)YM155?docetaxel(n=48)Docetaxel(n=51)Total(N=99) Any SAE25(52.1)17(33.3)42(42.4) HematologicFebrile neutropenia10(20.8)4(7.8)14(14.1) Neutropenia5(10.4)4(7.8)9(9.1) NonhematologicPneumonia3(6.3)2(3.9)5(5.1) SAE serious adverse eventpatient,the cause of death was unknown.None of the deaths were related to the study medications.Three patients discontinued treatment due to abnor-malities in laboratory values(increased gamma-glutamyl-transferase,increased blood urea nitrogen and blood creatinine,and platelet disorder/thrombopathy);all of these abnormalities were considered possibly or probably related to YM155.Other laboratoryfindings were generally not clinically significant.No cardiac safety signals were detected during the study.DiscussionFindings from this study of patients with HER2-negative metastatic breast cancer treated with YM155in combina-tion with docetaxel exhibited no statistically significant differences in the primary endpoint of PFS or secondary endpoints compared with patients administered docetaxel alone.The combination of YM155plus docetaxel was well tolerated.The most common drug-related TEAEs in the YM155plus docetaxel arm were expected and included neutropenia,fatigue,and febrile neutropenia.Renal failure was reported in a previous study with YM155and was considered to be related to YM155[23].In the present study,one patient in the combination arm discontinued with elevated blood urea nitrogen and creatinine levels that were deemed related to study drug;these events resolved 11and25days following onset,respectively.YM155was administered as a continuous intravenous infusion for168h in a21-day cycle.Preclinical data suggest that bolus infusion may increase the risk for renal and/or cardiovascular toxicity.Although continuous infu-sion is more time-consuming and may be less convenient, the need for continuous infusion did not affect recruitment in the present study,and patients experienced no difficulty with drug administration over a long period of time.An urgent unmet need for additional therapeutic options in patients with TNBC exists because of their high risk of relapse and poor long-term prognosis[24,25].A positive outcome was expected from this study because YM155is a novel drug that suppresses survivin at both the mRNA and protein levels[26];survivin is a protein that is associated with decreased apoptosis and has been shown to be more highly expressed in metastatic breast cancer compared with normal breast tissue[27].YM155is also highly distributed to tumor tissues relative to normal plasma[26].Although these preclinical data provide a good rationale for evalu-ating YM155in breast cancer,findings from the present study demonstrated that YM155plus docetaxel exhibited no statistically significant differences in PFS,ORR,OS, DOR,or CBR compared with patients administered doce-taxel alone.However,this study also had some limitations,including the lack of formal pharmacokinetic interaction analysis between YM155and docetaxel.In addition,the limited amount of biomarker data available leaves open the ques-tion of whether there is a patient population more likely to benefit from the combination of YM155with docetaxel. Improved availability and use of biomarkers could help identify patients with TNBC or other types of cancer who might benefit from specific inhibition of survivin.Although development of YM155in patients with TNBC is not proceeding,further research into drugs effective at target-ing the survivin pathway is warranted. Acknowledgments Funding for the study and editorial assistance in preparation of the manuscript was provided by Astellas.Editorial assistance was provided by Craig D.Albright,PhD,Anny S.Wu, PharmD,and Brett Mahon,PhD,of Complete Healthcare Commu-nications,Inc.(Chadds Ford,PA).Conflict of interest Michael R.Clemens has received research funding from Astellas.Oleg A.Gladkov,Elaina Gartner,and Vladi-mir Vladimirov have nothing to disclose.John Crown consulted for Astellas and received honoraria from Sanofi.Anne Keating,Fei Jie, and Joyce Steinberg are Astellas employees.Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per-mits any noncommercial use,distribution,and reproduction in any medium,provided the original author(s)and the source are credited. References1.Global Cancer Facts&Figures.(2011)American Cancer Society.Available via /acs/groups/content/@epide miologysurveilance/documents/document/acspc-027766.pdf.Accessed22May20142.Siegel R,Ma J,Zou Z,Jemal A(2014)Cancer statistics,2014.CA Cancer J Clin64:9–293.Cianfrocca M,Goldstein LJ(2004)Prognostic and predictivefactors in early-stage breast cancer.Oncologist9:606–6164.About Breast Cancer:Stages0and1(2012)National BreastCancer Foundation,Inc.Available via http://www.national /breast-cancer-stage-0-and-stage-1.Accessed15 May20145.Most common statistics cited for MBC(2014)Metastatic BreastCancer Network.Available via /education/cate gory/most-commonly-used-statistics-for-mbc.Accessed15May 20146.O’Shaughnessy J(2005)Extending survival with chemotherapyin metastatic breast cancer.Oncologist10(Suppl3):20–297.Coiffier B,Lepage E,Briere J,Herbrecht R,Tilly H,BouabdallahR,Morel P,Van Den Neste E,Salles G,Gaulard P,Reyes F, Lederlin P,Gisselbrecht C(2002)CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.N Engl J Med346:235–242 8.Chia SK,Speers CH,D’Yachkova Y,Kang A,Malfair-Taylor S,Barnett J,Coldman A,Gelmon KA,O’Reilly SE,Olivotto IA (2007)The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with meta-static breast cancer.Cancer110:973–979。
奥名润 多西他赛注射液使用说明书
通用名称：多西他赛注射液商品名称：奥名润汉语拼音：duoxitasaizhusheye批准文号：国药准字H20064301药品分类：化学药品生产企业：江苏奥赛康药业股份有限公司(国产)药品性质：处方药相关疾病：晚期乳腺癌,转移性乳腺癌,晚期非小细胞肺癌,转移性非小细胞肺癌, 性状：本品为淡橙黄色至橙黄色澄明液体。
主要成份：本品主要成份为多西他赛，其化学名为:[2aR-(2aα，4β，4aβ，6β，9α，(aR*，βS*)，11α，12α，12aα，12bα)]-β-[[(1，1-二甲基乙氧基)羰基]氨基]- α-羟基苯丙酸[12b-乙酰氧-12-苯甲酰氧-2a，。
，4，4a，5，6，9，10，11，12，12a，12b-十二氢-4，6，11-三羟基-4a，8，13，13-四甲基-5-氧代-7，11-亚甲基-1H-环癸五烯并-[3，4]苯并[1，2-b]氧杂丁环-9-基]酯。
适应症：1.多西他赛适于先期化疗失败的晚期或转移性乳腺癌的治疗。
除非属于临床禁忌，先期治疗应包括蒽环类抗癌药。
2.多西他赛适于使用以顺铂为主的化疗失败的晚期或转移性非小细胞肺癌的治疗。
规格：0.5ml∶20mg不良反应：1.骨髓抑制:中性粒细胞减少是最常见的副反应而且通常较严重（低于500个/mm3），可逆转且不蓄积。
2.过敏反应:部分病例可发生严重过敏反应，其特征为低血压与支气管痉挛，需要中断治疗。
停止滴注并立即治疗后病人可恢复正常。
部分病例也可发生轻度过敏反应。
如脸红，伴有或不伴有搔痒的红斑，胸闷，背痛，呼吸困难，药物热或寒战。
3.皮肤反应常表现为红斑，主要见于手?足，也可发生在臂部，脸部及胸部的局部皮疹，有时伴有搔痒。
皮疹通常可能在滴注多西他赛后一周内发生，但可在下次滴注前恢复。
严重症状如皮疹后出现脱皮则极少发生。
可能会发生指（趾）甲病变。
以色素沉着或变淡为特点，有时发生疼痛和指甲脱落。
4.体液潴留包括水肿，也有报道极少数病例发生胸腔积液，腹水，心包积液，毛细血管通透性增加以及体重增加。
多西他赛简介及抗肿瘤
多西他赛简介1.简介多西他赛（Docetaxol）是由欧洲浆果紫杉的针叶中提取的化合物半合成的紫杉醇衍生物，由法国的Rhone-Poulenc Rorer公司开发并上市。
其作用机理与紫杉醇类似，通过促进微管双聚体装配成微管，同时防止去多聚化过程而使微管稳定，阻滞细胞于G2和M期，抑制细胞进一步分裂，从而抑制癌细胞的有丝分裂和增殖。
多西他赛的药理作用比紫杉醇强，在细胞内浓度比紫杉醇高3倍，并在细胞内滞留时间长。
其对微管亲和力是紫杉醇的2倍；作为微管稳定剂和装配促进剂，活性比紫杉醇大2倍；作为微管解聚抑制剂，活性比紫杉醇大2倍。
在体外抗瘤活性试验中，已证实多西他赛的抗瘤活性是紫杉醇的1.3~12倍。
多烯紫杉醇抗瘤谱广、抗肿瘤作用强，对难治性的乳腺癌、非小细胞肺癌等的疗效均较突出，临床应用潜力深厚。
然而多西他赛难溶于水，且脂溶性也不大，严重影响了其临床应用。
目前上市品种仅为多西他赛注射液，是用吐温-80及乙醇作溶剂配制而成，易引起较多不良反应，如刺激、溶血、过敏反应、神经毒性、心血管毒性等等。
且使用前要使用抗过敏药物，给患者带来了极大的不便和痛苦。
本项目旨在解决多西他赛水溶性及稳定性问题，进而避免因使用吐温-80而引起的溶血、过敏等不良反应问题。
本项目的意义在于为临床提供一种安全有效的多西他赛静脉给药新制剂，同时对脂质体的制备工艺进行创新，在提高载药量的同时解决其稳定性问题，也为其它同性质药物制剂的制备提供借鉴作用。
2.研究现状及创新性中国专利CN1931157A公开一种可以注射或口服的多西他赛脂质体及其固体制剂。
其以磷脂、胆固醇为基本膜材，加入适当的附加剂，采用多种方法制备了各种类型的脂质体，制得的脂质体粒径小，包封率高，稳定性好且毒副作用低，基本达到了临床注射要求。
但制备的脂质体浓度较低，生产时需容积较大的容器，成本高，不适合大剂量给药。
抗肿瘤一、抗瘤谱多西他赛可用于乳腺癌，NSCLC（非小细胞肺癌），胰腺癌，软组织肉瘤，头颈癌，胃癌，卵巢癌，前列腺癌等。
多西他赛产品介绍完整版PPT
3.7%
CHF=充血性心衰
MBC--多西他赛单药治疗的III期
41个中心临床研究（TAX303）
结论：
在转移性乳腺癌治疗中，多西他赛是唯一显示出比 阿霉素有明显更高缓解率的单药
两组终点TTP相近，Doce.组26周VS阿组21周（p=0.45)
多西他赛具有可预期及 易于处理的安全特征，阿霉素 治疗的相关心脏毒性无法预期，不可逆，故其治疗组 有更多的毒性死亡
大规模，多中心临床试验证实： 多西他赛治疗转移性乳腺癌具有高度活性
多西他赛联合阿霉素是否可取代传统方案而成为 转移性乳腺癌的一线治疗？
国际多中心随机III期临床研究 （TAX306）
多西他赛+阿霉素与环磷酰胺+阿霉素 一线治疗转移性乳腺癌的疗效比较
（TAX306）研究设计
MBC患者分为：（50个中心） n=213 AD组：阿霉素50mg/m2+多西他赛75mg/ m2 n=210 AC组：阿霉素60mg/m2+环磷酰胺600mg/ m2 均为第一天给药，每21天为一周期
多西他赛，新一代半合成紫杉类衍生物
本品英文名：Docetaxel
主要成分：多西他赛（多西紫杉醇） 药理毒理： 体外实验表明，奥名润抗肿瘤谱广，对各类人移植性 肿瘤所造成的晚期小鼠肿瘤模型均有抗肿瘤活性 在克隆形成试验中，奥名润对新切除的肿瘤细胞也有
细胞毒作用 奥名润在细胞内浓度高且潴留时间长，对过度表达
--更高的疗效（ORR，TTP，TTF） --不增加阿霉素心脏毒性 --在预后较差的患者中维持更高的疗效
多西他赛/阿霉素（AT）是唯一被EU批准用于一线 治疗局部晚期或转移性乳腺癌的紫杉类联合化疗方案
多西他赛用于乳腺癌的辅助化疗中是否存在优势？
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
研发实力
专利
92项具有自主知识产权 的专利 其中有60项发明专利、 32项外观专利
批件
国家药监局颁发的83个药 品批准文号 其中化学药物注射剂68个、 原料药15个 新药证书21个
研发实力
研
Research & Development 机构
持续的研发投入，占销售 额约5% 自主筹建生物医药创新园
肿瘤的诊断
尽管肿瘤的生化、免疫和影像学诊断近年来有了很 大的发展，但是要确定是否是肿瘤、肿瘤的良恶性和恶 性程度，目前仍然要依赖病理学诊断。
病理学诊断被公认为是最后诊断，是金标准。
肿瘤的治疗
外科手术 放射治疗 化学治疗 介入治疗
综合治疗
中医治疗 物理疗法 内分泌治疗 诱导分化治疗
生物治疗
根据作用机制分类
iv,d1
iv,d1 21d为1个周期
po,bid d1～d14
原发性乳腺癌规范化诊疗指南（2019年）
前列腺癌
前列癌概况
前列腺癌是指发生在前列腺的上皮性恶性肿瘤 2019年我国前列腺癌发病率为9.92/10万，列男性恶性
肿瘤发病率的第6位。 发病年龄在55岁前较低，55岁后逐渐升高，发病率随
生产质量
严格化的原辅料质 量控制体系
精细化的原料药生 产过程
标准化的注射针剂 生产过程
规范化的产成品检 验标准
产品送检及市场抽 检合格率100%
质量源于设计
ASK的产品质量首先从产品设计开始，精益求精，关注细节， 并贯穿到每个过程的控制，已融入到新版GMP车间的过程管理中，
确保每个产品安全、有效
GMP认证 下一个目标：通过欧盟GMP认证！
Stephen Chan,et al.Journal of Clinical Oncology.2019;17(8):2341-2354
多西他赛单药治疗的III期41个 中心临床研究（TAX303）
研究结论：
在转移性乳腺癌治疗中，多西他赛与阿霉素相比显示 出有更高缓解率 在既往接受过化疗的乳腺癌患中，多西他赛较阿霉素 显著提高了有效率
缓解率：
治疗百分率 （%）
ITT治疗患者
多西他赛组 阿霉素组 （n=161） （ n= 165）
45.3
29.7
内脏转移患者 46.3
29.4
对其它化疗 47.4
24.7
方案耐药患者
Stephen Chan,et al.Journal of Clinical Oncology.2019;17(8):2341-2354
化疗方案 NP TP
GP
DP
药物
长春瑞滨 顺铂
紫杉醇 顺铂 或卡铂
吉西他滨 顺铂 或卡铂
多西他赛 顺铂 或卡铂
剂量（ mg/m2）
25 80 135-175 75 AUC=5-6 1250 75 AUC=5-6 75 75 AUC=5-6
用药时间
d1，d8 d1 d1 d1 d1
d1，d8 d1 d1 d1 d1 d1
缩写
CF MTX MIT L-OHP PTX,TAX DOC NVB Cap TPT ADM CBP NDP CDDP CTX
化疗药物的不良反应
骨髓抑制：白细胞、血小板下降 胃肠道毒性：恶心、呕吐（尤其烷化剂、抗代谢药
多见） 心脏毒性：心律失常、心肌炎等（蒽环类） 神经毒性：长春碱类、DDP、MTX和阿糖胞苷等引起
手术+辅助化疗
IIB T2，N1，M0 30 T3，N0-1，M0 40
手术+辅助化疗
IIIA T1-3，N2，M0 10-30 T3，N1，M0
手术+辅助化/放疗 或+新辅助化疗（N2）
IIIB Any T4,any N3,M0
<10
化疗或化疗+放疗
IV Any M1
<5
化疗+支持治疗
推荐NSCLC一线化疗方案
结构差异：多西紫杉醇与紫杉醇
相同点：紫杉类特征结构
4，5位：含O四环结构
不同点：
P：苯甲酰苯基 P：乙酰基
D：烷氧基 D：羟基
多西紫杉醇的取代基团空间 位阻小，极性基团亲水性强， 因此多西紫杉醇与微管蛋白
的亲和力是紫杉醇的2倍。
用法用量
多西他赛只能用于静脉滴注。 所有病人在接受多西他赛治疗期前均必须给予糖皮质激素类，如 地塞米松，在多西他赛滴注一天前服用，每天16mg，持续至少3 天，以预防过敏反应和体液潴留。 推荐剂量为75mg/m2滴注一小时，每三周一次。 临用前将多西他赛所对应的溶剂全部吸入对应的溶液中，轻轻振 摇混合均匀，将混合后的药瓶室温放置5分钟，然后检查溶液是否 均匀澄明，根据计算病人所用药量，用注射器吸入混合液，注入5 ％葡萄糖注射液或0.9％氯化钠注射液的注射瓶或注射袋中，轻轻 摇动，混合均匀，最终浓度不超过0.9mg/ml。
复发化疗方案 转移化疗方案
方案 TAC TC AC—T
FEC—T T AT XT
用量
多西他赛75mg/m2
多柔比星50mg/m2 环磷酰胺500mg/m2 多西他赛75mg/m2 环磷酰胺600mg/m2 多柔比星60mg/m2 环磷酰胺600mg/m2 序贯以多西他赛100mg/m2 氟尿嘧啶500mg/m2 表柔比星100mg/m2 环磷酰胺500mg/m2 序贯以多西他赛100mg/m2 多西他赛60～100mg/m2 多西他赛75mg/m2 多柔比星50mg/m2 多西他赛75mg/m2 卡培他滨950mg/m2
主要不良反应
骨髓抑制：中性粒细胞减少是最常见的副反应而且通常较严重（低于 500个/mm3），可逆转且不蓄积。
过敏反应：部分病例可发生严重过敏反应，其特征为低血压与支气管 痉挛，需要中断治疗。部分病例也可发生轻度过敏反应。如脸红，伴有 或不伴有搔痒的红斑，胸闷，背痛，呼吸困难，药物热或寒战。
体液潴留：经过4周期治疗或累积剂量达400mg/m2后，发生液体潴留， 并可能发展至全身水肿。为了减少液体潴留，应给病人预防性使用皮质 类固醇。
早期辅助化疗、 术前新辅助化疗、 术后辅助化疗等
治疗方法
改良根治术、保乳术、 区段切除、乳房重建等
部分乳房照射、 短程放疗、乳腺 切除术后放疗 和放疗、化疗序贯等
个体化 综合治疗
雌激素受体 拮抗剂三苯氧胺、 芳香化酶抑制剂等
分子靶向： 曲妥珠单抗等
推荐乳腺癌化疗方案
分期
辅助化疗方案 新辅助化疗方案
奥名润产品介绍
市场部 2019-10-15
内容概要
奥赛康企业介绍 肿瘤产品知识
奥名润产品介绍
奥赛康企业介绍
发展历程
● 创办 南京海光应用化学研究所
1992年
● 成立 江苏奥赛康药业有限公司
2019年
● 股份制改造，更名为 江苏奥赛康药业股份有限公司
2019年
2019年
● 成立 扬州奥赛康药业有限公司
奥名润产品介绍
奥名润
2019/9/23
多西他赛作用机制
独特的作用机制：多西他赛属微管解聚抑制剂 促使微管蛋白聚合成微管，同时抑制微管的解聚，从而抑制了 细胞的有丝分裂和增殖。 多西他赛的这种细胞毒作用与紫杉醇相似，但稳定微管作用 比紫杉醇大2倍，治疗瘤谱也较紫杉醇更广
多西他赛在乳腺癌的临床应用
多西他赛治疗转移性乳腺癌的里程碑研究
• 多西他赛单药的里程碑研究 – 多西他赛vs. 阿霉素 TAX303 – 多西他赛vs. 紫杉醇 TAX311
• 多西他赛联合方案的里程碑研究 – 多西他赛+阿霉素 vs. 环磷酰胺+阿霉素 TAX306
TAX303
多西他赛单药治疗的III期41个 中心临床研究（TAX303）
时间及周期 q21d×4 q21d×4 q21d×4 q21d×4
卫生部《原发性肺癌诊疗规范》2019版
乳腺癌
乳腺癌概况
全球每年约有120万妇女患乳腺癌，50万人死于乳腺癌 近10年来，我国的乳腺癌发病率上升了3.8%，上海、武汉天津、 北京、哈尔滨、等地的发病率都占到当地女性恶性肿瘤的第一、 二位，死亡率为13.1-8.7/10万 发病年龄始于30岁，高峰在40-49岁 就诊时的病期相对偏晚
2019年
● 成立 南京奥赛康医药集团
国家级荣誉
公司荣誉
公司荣誉
连续五年获得“中国医药研发产品线最佳工业企业”
2019年
2019年
2019年
2019年
2019年
产品概况
全国抗肿瘤药品种最多的企业之一
全国PPI针剂品种最全的企业之一
抗肿瘤类——铂类为主的抗肿瘤产品和抗肿瘤辅助用药产品组合群
消化类——PPI注射剂产品组群
慢性神经毒性；环磷酰胺、氟尿嘧啶、引起的神经 病变常是急性或亚急性的。 ……
肺癌
肺癌概况
肺癌发病率在大多数国家有明显增高的趋势，在发达国家 中在男性恶性肿瘤占首位，女性恶性肿瘤占第2、3位，亦 是最常见的死亡率最高的恶性肿瘤
从我国分布来看，上海、北京、东北和沿海几个大城市的 死亡率最高
其他产品
其他产品
肿瘤产品群
PPI产品群
铂类主要适应症： 头颈部癌，小细胞肺癌，非小细胞肺癌，食管癌等实体瘤 经氟尿嘧啶治疗失败后已转移的结直肠癌
辅助用药奥诺先主要适应症：
预防和治疗对蒽环类药物有心脏不良反应的女性乳腺癌患者
PPI主要适应症：
急性上消化道，消化性溃疡出血，吻合口溃疡出血 预防重症疾病（如脑出血、严重创伤等）应激状态及胃
研究方案： 多西他赛 100mg/m2 q3wks, 静滴 阿霉素 75mg/m2 q3wks，静滴
Stephen Chan,et al.Journal of Clinical Oncology.2019;17(8):2341-2354