顺糖氨铂(Ⅱ)的合成

以氯铂酸钾为原料，经硫酸氨铂(Ⅱ)中间体制得抗肿瘤药物顺糖氨铂(Ⅱ)，操作简便，总收率46．1％。     

奈达铂（Nedaplatin）在大鼠体内的肾毒性和骨髓抑制的时辰毒理学研究

目的:以大鼠为实验对象,通过测定给药时间与奈达铂(Nedaplatin)诱发的肾毒性和骨髓抑制的关系,研究铂(Pt)衍生物奈达铂的时辰毒理.方法:于8:00或20:00通过尾静脉给S-D大鼠(n=8)注射奈达铂(5 mg/kg体重)或空白溶媒,给药间隔为7天.定期采血、采尿测定血清肌苷清除率和周边血中的中性粒细胞.最后一次给药后24小时,处死动物,采集肾脏和大腿骨用于Pt浓度测定和组织学检查.共给药6次.结果:20:00给药组的体重抑制明显高于8:00给药组,实验结束时,两实验组均有2只动物死亡.奈达铂诱发的骨髓抑制没有明显的给药时间相关性,但20:00给药组的肾毒性明显大于8:00给药组.肌苷清除率和肾组织损伤积分均与肾皮质中n的含量有很好的相关性.结论:奈达铂诱发的肾毒性和药物在组织中的蓄积与给药时间有很好的相关性,提示该类药物在临床使用过程中应注意给药时间的选择.     

紫杉醇脂质体和紫杉醇在晚期食管癌治疗中的临床研究

目的：比较紫杉醇脂质体和紫杉醇治疗晚期食管癌的安全性及临床疗效。方法将该科近3年收治的90例晚期食管癌患者分为2组。紫杉醇脂质体组（试验组）45例给予紫杉醇脂质体80 mg／m2静脉滴注,第1、8天;奈达铂75 mg／m2静脉滴注,第1天。紫杉醇组（对照组）45例给予紫杉醇80 mg／m2,静脉滴注,第1、8天;奈达铂75 mg／m2,静脉滴注,第1天。3周为1个周期,化疗2个周期后按WHO标准进行评估近期疗效及不良反应。结果近期疗效方面,紫杉醇脂质体和紫杉醇相比较,差异无统计学意义（P＞0．05）,但在紫杉醇溶媒产生的过敏反应方面,试验组明显低于对照组,差异有统计学意义（P＜0．05）。结论紫杉醇脂质体或紫杉醇联合奈达铂治疗晚期食管癌疗效确切,两种紫杉醇疗效相当,但紫杉醇脂质体的过敏反应明显低于紫杉醇,值得临床推广。     

顺铂或奈达铂联合紫杉醇治疗宫颈癌的疗效比较

目的 对比分析顺铂或奈达铂与紫醇联合治疗宫颈癌的疗效。方法 选择2012年2月-2015年12月在宁强县天津医院进行诊治的宫颈癌患者160例,按照使用化疗药物的不同分为顺铂组和奈达铂组。顺铂组采取TP化疗方案,奈达铂组采取TN化疗方案,对比两组的疗效、化疗不良反应、住院时间和治疗费用。结果 顺铂组的有效率为79.26%,与奈达铂组的82.05%相比无明显差异;奈达铂组Ⅰ~Ⅳ级血红蛋白降低、白细胞减少的发生率均明显高于顺铂组（P<0.05）,但两组间Ⅲ~Ⅳ级血红蛋白降低、血小板和白细胞减少发生率无明显差异,奈达铂组Ⅰ~Ⅳ级和Ⅲ~Ⅳ级恶心、呕吐发生率均明显低于顺铂组（P<0.05）;奈达铂组患者的住院时间明显短于顺铂组（P<0.05）;奈达铂组的治疗费用与顺铂组相比无明显差异。结论 顺铂或奈达铂与紫杉醇联合应用于宫颈癌辅助化疗的疗效相似,奈达铂的胃肠道不良反应比顺铂更低,骨髓抑制尽管增加但仍可控,采用奈达铂化疗较顺铂缩短了住院时间,且住院费用并无明显增加,患者更易接受。     

吉西他滨联合奈达铂治疗复发性宫颈癌的临床疗效

目的 研究吉西他滨联合奈达铂治疗复发性宫颈癌的疗效和安全性。方法 将2012年2月-2014年1月上海交通大学附属第六人民医院收治的98例宫颈癌复发患者作为研究对象,通过随机抽样分为治疗组和对照组,每组各49例。治疗组静脉滴注注射用吉西他滨1 g/m²加入0.9%生理盐水100 mL,持续30 min,每个化疗周期前3周的第1天使用;注射用奈达铂80 mg/m²用0.9%生理盐水稀释至500 mL后静脉滴注,滴注时间至少为60 min,每个周期的第1周第1天时使用。对照组吉西他滨使用方法与治疗组一致;注射用顺铂30 mg/m²注入0.9%生理盐水30 mL后静脉滴注,每个周期的第1周前3 d时每天使用。两组都以28 d为1个疗程,并至少治疗2个疗程。治疗结束后,比较两组的临床疗效和毒副作用情况。结果 治疗组和对照组治疗有效率分别为63.27%、55.10%,两组比较差异无统计学意义。在毒副作用方上,两组脱发、白细胞下降、心脏毒性、肺毒性、肝损害以及皮疹的发生率差异无统计学意义。治疗组血小板降低发生率高于对照组,但在恶心呕吐、血红蛋白下降和肾脏损害的发生率均明显低于对照组,两组比较差异有统计学意义（P<0.05）。结论 吉西他滨联合奈达铂或顺铂治疗复发性宫颈癌的临床疗效无差异,但吉西他滨联合奈达铂的毒副反应较小,有利于减少患者化疗痛苦,提高患者依从性。     

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。     

奈达铂联合三维适形放射治疗晚期食管癌

目的探讨奈达铂(NDB)联合三维适形放射(3DCRT)方法治疗晚期食管癌的近期疗效、生存期及毒性反应。方法90例食管癌病人根据入选标准,随机分组,46例进入3DCRT+NDB组(试验组),44例进入单纯3DCRT组(对照组)。NDB按80～100 mg·m~(-2)+氯化钠注射液500 mL静脉滴注2h, d1,28d为一个周期,共行3个周期。先进行1个周期化疗后开始3DCRT,每次5～6 Gy,隔日照射1次,共7～8次,总剂量40～42 Gy(13～15d)。结果有效率试验组为91%,对照组为71%(P< 0.05);1、2、3年局部控制率试验组分别为76%、70%和50%,对照组分别为45%、34%和20% (P<0.05);1、2、3年生存率试验组分别为72%、59%和50%,对照组分别为41%、36%和25% (P<0.05)。试验组的白细胞下降及血小板减少发生率较对照组高(P<0.05;P<0.01),但病人均能耐受。结论以NDB单药联合3DCRT治疗能明显改善晚期食管癌生存率和局部控制率,虽不良反应增加但均能耐受。     

Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer

To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with gemcitabine, and to observe their antitumour activity, we conducted a combination phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8, every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC who received no prior chemotherapy or one previous chemotherapy regimen were enrolled. The most frequent toxicities were neutropenia and thrombocytopenia; nonhaematological toxicities were generally mild. Three out of six patients experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine, which was regarded as the MTD. There were three partial responses, for an overall response rate of 16.7%. The median survival time and 1-year survival rate were 9.1 months and 34.1%, respectively. This combination is well tolerated and active for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and further evaluation in prospective randomised trials with cisplatin- or carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.     

Weekly paclitaxel and nedaplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a phase I/II study

OBJECTIVE: The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC). METHODS: Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The RT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated. RESULTS: Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1. CONCLUSION: Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.