XELOX与DF方案治疗晚期胃癌临床疗效比较

目的比较XELOX和DF方案对晚期胃癌的临床疗效和毒副反应。方法132例晚期胃癌患者随机分为XELOX组和DF组。所有病例治疗4周期以上,按WHO标准评价并比较两组的客观疗效和毒副反应。结果XELOX组总有效率52．3％,DF组总有效率47．8％（P〉0．05）。XELOX组手足综合征的发生率为36．92％,明显高于DF组的13．43％（P〈0．05）;而骨髓抑制的发生率为41．54％,显著低于DF组的85．07％（P〈0．05）;其余各项常见的副作用未见明显差异,无统计学意义（P〉0．05）。结论XELOX方案与DF方案治疗晚期胃癌疗效相当,而XELOX方案骨髓抑制副反应小,耐受性好,更易为老年患者所接受。     

多西紫杉醇为主的两药联合方案与三药联合方案一线治疗国人晚期胃癌的疗效比较

目的 分析比较多西紫杉醇（TXT）为主的两药联合方案和三药联合方案一线治疗国人晚期胃癌的有效性与安全性。方法 收集2009年1月至2012年1月收治的46例初治晚期胃癌患者,包括20例应用三药联合的改良DCF方案（三药联合组）和26例应用两药联合的DC或DF方案（两药联合组）。三药联合组具体为：TXT 30mg／m2静滴,d1、d8;顺铂（DDP）20mg静滴,d1～d5;氟尿嘧啶（5-FU）500mg／m2静滴,d1～d5,21天为1周期。两药联合组具体为：TXT 37.5mg／m2静滴,d1、d8;DDP 20mg静滴,d1～d5或5-FU 500mg／m2静滴,d1～d5,21天为1周期。化疗2个周期后按照RECIST 1.0标准评价疗效,按NCI CTC 30版评价毒副反应并随访生存情况。结果 46例患者中有45例可评价客观疗效,46例均可评价不良反应。三药联合组和两药联合组的有效率（RR）分别为31.6％和26.9％,疾病控制率（DCR）分别为68.4％和57.7％,中位肿瘤进展时间（TTP）分别为5.2个月和4.5个月,中位生存时间（OS）分别为10.0个月和9.1个月,以上差异均无统计学意义（P＞0.05）。两组不良反应均可耐受,主要为乏力、骨髓抑制、黏膜炎,大多为1～2级,3～4级少见;但两药联合组乏力、骨髓抑制及黏膜炎的发生率均低于三药联合组,差异有统计学意义（P＜0.05）。结论 在采用TXT为主的联合方案一线治疗国人晚期胃癌时,两药联合方案与三药联合方案的疗效相当,且两药方案耐受性更好,值得临床重视。     

比卡鲁胺联合化疗治疗去势抵抗性前列腺癌的临床分析

目的探讨晚期去势抵抗性前列腺癌安全、有效的治疗方法。方法以比卡鲁胺作为二线抗雄激素药物,联合多西紫杉醇加泼尼松化疗治疗26例去势抵抗性前列腺癌患者,观察疗效及毒副反应。结果 26例去势抵抗性前列腺癌患者25例有效,有效率为96.15%。最常见的毒副反应是骨髓抑制,可耐受。结论比卡鲁胺作为二线抗雄激素药物联合多西紫杉醇加泼尼松化疗治疗去势抵抗性前列腺癌的临床疗效明显,毒副反应轻,可作为晚期去势抵抗性前列腺癌的治疗策略。     

多西他赛联合泼尼松治疗激素难治性前列腺癌

目的 观察多西他赛联合泼尼松3周方案治疗激素难治性前列腺癌的疗效.方法 2004年9月至2007年1月对13例激素难治性前列腺癌患者行多西他赛联合泼尼松3周方案化疗.患者69～82岁,平均75岁.入选标准：全雄激素阻断治疗失败,排除抗雄激素撤除综合症,并至少经过1次抗雄药物撤退以外的二线内分泌治疗无效.治疗方案：化疗第一天用多西他赛75 mg/m2,泼尼松5 mg,2次/d;从化疗第二天起泼尼松5 mg,2次/d,连续应用,21 d为1疗程.观察终点为血PSA、可测量病灶和疼痛的变化.结果 13例入组患者中1例失访,11例可评价疗效,PSA有效率为54%（6/11）,有效患者PSA从治疗前的23.6 ng/ml、515.5 ng/ml、150.0 ng/ml、16.4 ng/ml、152.7 ng/ml、12.3 ng/ml,下降到治疗后最低2.4 ng/ml、139.9 ng/ml、42.3 ng/ml、6.7 ng/ml、67.5 ng/ml、5.7 ng/ml.有效持续时间4个月、3个月、8个月、3个月、2个月、2个月.可测量病灶2例为稳定.骨痛改善率为50%（3/6）.12例可评价不良反应,主要不良反应为骨髓抑制,Ⅲ度白细胞减少占50%.12例中位随访194 d.死亡5例,已死亡患者从诊断激素非依赖性前列腺癌起中位生存期36个月.结论 多西他赛联合泼尼松3周方案治疗激素难治性前列腺癌有一定疗效,毒性可耐受.     

吉非替尼与多西紫杉醇二线治疗非小细胞肺癌的疗效比较

目的 探讨吉非替尼与多西紫杉醇单药作为二线治疗对晚期非小细胞肺癌的疗效和不良反应.方法 将既往一线化疗失败的51例晚期非小细胞肺癌患者,分为吉非替尼组和国产多西紫杉醇组进行治疗观察.结果 吉非替尼组临床获益率为53.8%,一年生存率为34.6%;国产多西紫杉醇组临床获益率为48%,一年生存率为28%.两组临床获益比较差异无显著性(P＞0.05),但吉非替尼组血液毒副反应明显小于多西紫杉醇组,生活质量评分改善率更高(P＜0.05).结论 对化疗失败的晚期非小细胞肺癌,吉非替尼单药疗效与多西紫杉醇单药疗效相近,但不良反应更轻,对生活质量改善率更高.     

Antiproliferative activity of bortezomib alone and in combination with cisplatin or docetaxel in head and neck squamous cell carcinoma cell lines

Purpose

Proteasome inhibition has been shown to be effective in multiple myeloma and solid tumor models. In this in vitro study, we investigated the antitumor effect of bortezomib (Velcade^®) in squamous cell carcinoma of the head and neck (SCCHN) cell lines and examined the interaction of the drug with docetaxel (TAX) and cisplatin (CDDP).

Methods

Dose escalation studies were performed with eight squamous cell carcinoma cell lines using bortezomib alone or in combination with TAX or CDDP. Growth inhibitory and proapoptotic effects were measured quantitatively using cytohistology and western blot analysis.

Results

Bortezomib alone showed a significant antiproliferative activity in all SCCHN cell lines (P = 0.012), and the activity was further enhanced by the addition of TAX or CDDP (P ≤ 0.036). When the combination of bortezomib and CDDP was used, the dose of the latter could be reduced to yield the same antiproliferative effect as the cytotoxic drug alone (P < 0.012).

Conclusions

Our results indicate that bortezomib increases the cytotoxic activity of TAX and CDDP in SCCHN cell lines. In vivo and in the clinical setting, the addition of bortezomib may allow to reduce the doses of TAX or CDDP to decrease the systemic toxicity of these drugs.

     

Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy

Nanoparticle (NP) drug loading is one of the key defining characteristics of an NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT^®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel.     

Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy

A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.