奈达铂联合多西他赛治疗晚期食道癌的临床观察

目的：观察奈达铂联合多西他赛治疗晚期食道癌的近期疗效及不良反应。方法：将80例晚期食道癌患者随机分为治疗组和对照组,每组40例,治疗组：采用奈达铂联合多西他赛治疗,其中奈达铂25mg／（m2·d）第1～3天给予;对照组：采用顺铂联合多西他赛治疗,其中顺铂25mg／（m2·d）第1～3天给予,两组均在第1天给予多西他赛75mg／m2,21天为1个周期。化疗2个周期后按WHO标准评价疗效及毒副作用。结果：治疗组完全缓解2例,部分缓解14例,稳定18例,进展6例,有效率为40．0％（16／40）;对照组完全缓解2例,部分缓解16例,稳定16例,进展6例,有效率45．0％（18／40）,两组有效率比较差异无统计学意义（P〉0．05）。治疗组和对照组消化道不良反应分别为10．0％和30．0％;肾毒性分别为0和15．0％,血小板下降分别为30．0％和5．0％,差异有统计学意义（P〈0．05）;白细胞减少分别为70．0％和65．0％,差异无统计学意义（P〉0．05）。结论：奈达铂联合多西他赛方案与顺铂联合多西他赛方案治疗晚期食道癌的疗效相近,在毒副作用方面多西他赛联合奈达铂方案耐受性良好,具有优势。     

Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated with induction of cytochrome P450 3A1/2

Abstract

1.?Triacontanol was confirmed to have a potential anti-cancer effect, the aim was to assess whether the co-administration of triacontanol alters the exposure of docetaxel via inducing hepatic CYP3A1/2 activity. The concentration of docetaxel in rats pretreated with triacontanol for seven successive days was determined, and the expression levels of CYP3A protein and mRNA were analyzed by the western blot and real time polymerase chain reaction (RT-PCR) technique, respectively.

2.?The concentrations of docetaxel in rats pretreated with triacontanol were decreased, with 61.5%, 61.9% decrease in AUC_0–24h and 65.7%, 54.9% reduction in C_max (120 and 180?mg?kg^?1, respectively) compared with the control. Hepatic clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180?mg?kg^?1, and CYP3A activity was up-regulated by measuring the formation rate of 1-hydroxymidazolam. Triacontanol preferentially induced protein expression level of CYP3A2 in a dose-dependent manner and of CYP 3A1 at dosage of 120 and 180?mg?kg^?1. The mRNA expression of CYP3A1 was moderately different with the western blot results, but the trends appeared similar. CYP3A2 mRNA level was not markedly affected by triacontanol.

3.?The significant triacontanol–docetaxel interaction was largely due to the induction of CYP3A1/2, which brought useful information in the clinical therapy when the combination is administered in human.     

注射用多西他赛纳米粒在犬体内的药动学研究

目的建立高通量测定犬血浆中多西他赛浓度的液相色谱-串联质谱(LC-MS/MS)方法,并将其应用于注射用多西他寒纳米粒与多西他赛注射液的药动学比较研究。方法2组Beagle犬分别前肢静脉注射5 mg·kg~(-1)的注射用多西他赛纳米粒和多西他赛注射液后,后肢静脉取血约0.5 mL。血浆样品及内标紫杉醇置于96孔板中,采用8道移液器取液进行高通量的液液萃取。采用LC-MS/MS法测定血药浓度,计算主要药动学参数。结果多西他赛的线性范围为1～500μg·L~(-1),最低定量限为1μg·L~(-1),提取回收率均大于95%,批内、批问精密度(RSD)均小于15%。注射用多西他赛纳米粒和多西他赛注射液,t_(1/2)分别为(5.3±s 1.4)和(3.2±1.4)h,MRT分别为(3.2±1.3)和(0.66±0.21)h,V_(ss)分别为(83±48)和(15±6)L,且2种制剂的t_(1/2)、MRT和V_(ss)均具有显著差异。结论该方法灵敏、准确、专一、简便并且实现高通量分析,适用于多西他赛的药动学比较研究。与多西他赛注射液相比,注射用多西他赛纳米粒能控制药物释放速率,并具有较长的体内循环时间,在一定程度上控制了急性毒性,提高机体耐受性。     

滤膜法测定多西紫杉醇脂质体的包封率

目的 建立多西紫杉醇脂质体包封率测定方法.方法 多西紫杉醇的含量测定采用HPLC,色谱柱为Lichrospher-RP C18柱(150 mm×6.0 mm,5 μm),流相为乙腈-水(60∶40),流速为1.0 mL·min-1,检测波长为231 nm,柱温为35 ℃.利用0 22 μm微孔滤膜分离脂质体与游离药物,考察滤膜法测定脂质体包封率的可行性.结果 该色谱条件下,多西紫杉醇得到良好分离,辅料不干扰药物的测定,各指标均符合测定要求.0 22 μm微孔滤膜截留作用明显,能有效分离游离药物与载药脂质体.结论 滤膜法简便、快捷,非常适合于多西紫杉醇脂质体的包封率测定.     

半人工合成手性多西紫杉醇对肺腺癌细胞株A549的细胞毒性及放射增敏作用

目的:探讨半人工合成手性多西紫杉醇对人肺癌细胞株A549的细胞毒性及放射增敏作用。方法:半人工合成手性多西紫杉醇,测定其对A549细胞的生长抑制作用,观察其对A549细胞的形态学影响及其放射增敏作用和对动物荷瘤模型的作用。结果:不同浓度半人工合成紫杉醇对A549细胞均有抑制作用,可引起A549细胞G2/M期阻滞,抑制荷瘤小鼠模型肿瘤的生长,其中空白对照组、单纯药物组、单纯放射组和联合处理组的肿瘤体积分别为(7780±1050)mm3、(4610±950)mm3、(5540±1035)mm3和(560±112.5)mm3,各组间有明显差异。结论:半人工合成紫杉醇对A549细胞株具有明显的抑制作用,且与射线照射有协同作用。     

再放疗并同步使用Docetaxel在鼻咽癌放疗后复发病人中的应用

目的:不能手术切除的鼻咽癌放疗后再复发的病人,其治疗困难,化疗疗效差,而单独再放疗只能挽救一小部分病人,本文探讨再放疗并同步使用多西紫彬醇(Docetaxel)在鼻咽癌首次放疗后复发病人中可行性及毒副反应,并评价其疗效。方法:对11例鼻咽癌足量放疗后经组织病理学证实复发、而无法行手术及腔内放疗的患者进行了同步放化疗。放疗采用三维适形放疗,外照射鼻咽部,分次量为1.8Gy,总剂量为36Gy-39.6Gy。化疗采用Docetaxel,15mg/m2,每周一次,静脉滴注。结果:10%、33%的患者分别出现Ⅲ度、Ⅳ度皮肤反应,18%、10%的病人分别出现Ⅲ度、Ⅳ度黏膜反应,18%患者出现Ⅲ度恶心呕吐,27%的患者出现Ⅲ度-Ⅳ度白细胞下降,10%患者出现Ⅲ度血小板下降。1例患者因严重的黏膜反应致使治疗延迟2周。治疗结束后,9例(82%)患者达到CR,2例(18%)达到PR,反应率为100%。结论:对于放疗后局部复发的鼻咽癌患者,采用同步放化疗,3D-CRT同时每周使用Docetaxel是可行的,其毒性反应在可以接受的范围内,短期疗效显著。     

多西紫杉醇联合长春瑞滨治疗蒽环类耐药性转移性乳腺癌的疗效分析

目的：观察多西紫杉醇、长春瑞滨联合方案在对蒽环类耐药转移性乳腺癌治疗中的疗效及不良反应。方法：蒽环类耐药性转移性乳腺癌35例，予多西紫杉醇联合长春瑞滨化疗，21天为1周期，至少用2周期。用世界卫生组织的疗效和抗肿瘤药急性及亚急性毒性反应分度标准评价疗效及毒性。结果：在35例可评价疗效的患者中，完全缓解10例，部分缓解13例，有效率为65．7％，临床获益率91．4％。不良反应主要骨髓抑制、脱发、消化道反应，但均可耐受，无化疗相关死亡。结论：该方案治疗蒽环类耐药性转移性乳腺癌患者，疗效较好，不良反应可耐受。     

多西他赛联合顺铂治疗晚期食管癌临床观察

为了观察多西他赛联合顺铂(DDP)化疗方案治疗晚期食管癌的近期疗效和不良反应,制定化疗方案如下:多西他赛60mg/m2,静脉滴入1h,d1;DDP30mg/m2,静脉滴入,d2～d4。21d为1个周期,完成3个周期后判定疗效。全组病例110例:初治78例有效率46%(36/78),复治32例,有效率25%(8/32),总有效率40%(44/110)。主要毒副反应为恶心、呕吐和骨髓抑制。初步研究结果提示,多西他赛联合DDP是治疗晚期食管癌有效且毒性较少的联合化疗方案。     

Emerging therapeutic options for breast cancer chemotherapy during pregnancy.

BACKGROUND: Breast cancer is the commonest solid tumor observed during pregnancy. Anthracycline-based chemotherapy is feasible during the 2nd and 3rd trimesters of pregnancy, but few data are available on recent and highly active drugs taxanes, vinorelbine and anti-HER-2 agents in this setting. PATIENTS AND METHODS: We carried out a comprehensive review of reports documenting the use of taxanes, vinorelbine, trastuzumab and lapatinib during pregnancy in the English literature, in order to evaluate their safety profile in pregnant patients. RESULTS: Twenty-four pregnancies are described, in which no grade 3-4 maternal toxicity nor malformation in the offspring was reported. Whereas only one report studied the pharmacokinetics of paclitaxel (Taxol) during pregnancy, several preclinical reports indicate that the placental P-glycoprotein could prevent the transplacental transfer of taxanes and vinorelbine. The use of trastuzumab was associated with the occurrence of anhydramnios in three of six cases. CONCLUSION: The administration of recent drugs taxanes and vinorelbine seems feasible during the 2nd and 3rd trimesters of pregnancy, with a favorable toxicity profile. In contrast, anti-HER-2 agents may obscure the normal development of the fetal kidney, and should be avoided during pregnancy.