RP—HPLC法测定大鼠血浆中洛铂的浓度

目的：建立测定大鼠血浆中洛铂血药浓度的方法。方法：取10只大鼠尾静脉注射洛铂10．64mg／kg后即刻取血分离血浆,采用反相高效液相色谱法测定血药浓度。色谱柱为Diamonsil流动相为乙腈．水（13．5：86．5）,流速为1．0ml／min,检测波长为210NM,柱温为35℃,进样量为20肛l。结果：洛铂的保留时间为5．13rain;其检测质量浓度的线性范围为O．5～80．0μg／ml（R=O．9999）,定量限为0．5μg／ml,方法回收率为（96．61±4．04）％～（107．9±6．76）％,日内KSD为2．43％～5．43％（n=5）,日间RSD为2．39％～8．93％（n=5）;平均血药浓度为（67．43±10．45）肛g／m1。结论：本方法操作简便、准确、灵敏度高,可用于大鼠血浆中洛铂的血药浓度测定。     

洛铂联合吉西他滨治疗晚期胰腺癌临床观察

目的观察洛铂联合吉西他滨治疗晚期胰腺癌的t临床疗效及不良反应。方法30例晚期胰腺癌患者随机分为两组,观察组18例,给予GP方案（洛铂联合吉西他滨）,21d为1个周期;对照组12例,给予GEMOX方案（奥沙利铂联合吉西他滨）,21d为1个周期,均至少化疗2个周期。结果30例患者均可评价疗效和不良反应。观察组临床受益反应率明显优于对照组（53％vs32％,P〈0．05）;观察组中位生存期和1年生存率也明显优于对照组（P〈0．05）;主要不良反应（血小板减少、胃肠道反应、末梢神经炎）较对照组轻,其他不良反应两组相似,患者均可耐受。结论洛铂联合吉西他滨治疗晚期胰腺癌近期临床疗效较高,不良反应可以耐受。     

洛铂或顺铂联合依托泊苷治疗初治小细胞肺癌临床疗效的观察

目的评价洛铂联合依托泊苷化疗方案(EL方案)治疗初治小细胞肺癌(SCLC)的近期疗效和不良反应,并与顺铂联合依托泊苷化疗方案(EP方案)对比。方法选择2011年6月至2012年1月我科收治的51例初治小细胞肺癌患者为研究对象,所有患者均经病理组织学或细胞学确诊,洛铂组采用EL方案,即洛铂30mg·m-2静滴,d1;依托泊苷100mg·m-2静滴,d1～3;3周为1周期。顺铂组采用EP方案,即顺铂25mg·m-2静滴,d1～3;依托泊苷剂量及用法同洛铂组,21d为1周期,连续用药2周期以上。参照RECIST1.1和CTCAE-3标准评价近期疗效和不良反应。结果洛铂组1例(4.5%)完全缓解,11例(50.0%)部分缓解,治疗总有效率为54.5%,顺铂组1例(3.4%)完全缓解,19例(65.5%)部分缓解,治疗总有效率为68.9%,两组间差异无统计学意义(P=0.291)。洛铂组Ⅲ～Ⅳ度血小板降低发生率(2例,9.1%)高于顺铂组(1例,3.4%),但差异无统计学意义(P=0.396)。洛铂组Ⅲ～Ⅳ度胃肠道反应(1例,4.5%)明显低于顺铂组(8例,27.6%),差异有统计学意义(P=0.033)。结论 EL方案与EP方案治疗初治小细胞肺癌的疗效相似,血小板降低作用增加,但胃肠道反应较轻,安全耐受性好。     

洛铂联合伊立替康治疗广泛期小细胞肺癌的临床观察

目的：评价洛铂联合伊立替康治疗广泛期小细胞肺癌的临床疗效和安全性。方法：洛铂35mg／m。第1天,伊立替康80mg／m。第1、8天,每21d为一周期,每2个周期结束复查影像学资料行疗效评价,治疗既往未接受过化疗的广泛期小细胞肺癌25例。结果：25例患者均可评价疗效,完全缓解（CR）1例,部分缓解（PR）9例,稳定（SD）7例,进展（PD）8例。客观缓解率（ORR）40％,疾病控制率（DCR）68％,中位无进展生存期（PFS）5．3个月,中位生存期（OS）7．6个月,主要毒副反应为血液学毒性及消化道反应。结论：洛铂联合伊立替康方案作为广泛期SCI。C化疗有较好的疗效,毒副反应可以耐受。     

Lobaplatin suppresses proliferation and induces apoptosis in the human colorectal carcinoma cell Line LOVO in vitro

Lobaplatin, as the third-generation platinum antineoplastic agent, showed promising antineoplastic effects in variety of preclinical test tumor models. We investigated the inhibition effect of lobaplatin on the colorectal carcinoma cell line LOVO in vitro, and explored its mechanism of action. The MTT assay was used to determine the inhibitory effect and inhibition ratio of lobaplatin on LOVO at various lobaplatin concentrations (500 μM, 1000 μM, 2000 μM). Apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP nickend labelling (TUNEL). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3,8,9 in cells was detected by chromometry. The results of MTT assay showed that proliferation of LOVO cells was inhibited by lobaplatin in a concentration-dependent manner. Apoptosis was detected in LOVO cells by TUNEL. The FCM assay indicated that lobaplatin altered the cell cycle and induced apoptosis of the LOVO cells when treated for 24 h, the percentages of cells in the S phase transition were increased, whereas the percentages of cells in the G₂ transition were decreased. The expressions of caspase-389 is higher than the control group after LOVO cells were treated by lobaplatin. Lobaplatin can inhibit the proliferation of colorectal carcinoma cell line LOVO by inducing apoptosis in vitro. The mechanism may be related to the “S” cycle arrest in cell cycle distribution and the up-regulated expression of caspase-8 and caspase-9 which up-regulated the expression of caspase-3.     

洛铂联合阿霉素、异环磷酰胺化疗方案新辅助治疗骨肉瘤的剂量探索

目的 探讨洛铂（LBP）联合阿霉素（ADM）、异环磷酰胺（IFO）化疗方案新辅助治疗骨肉瘤的最大耐受量（MTD）,并观察其毒副反应。方法 LBP设定3个剂量水平,分别为45mg／m²、50mg／m²、55mg／m²,ADM和IFO剂量固定（ADM 60mg／m²、IFO 12g／m²）,观察到出现剂量限制性毒性（DLT）即终止试验,或至55mg／m²未出现DLT,试验亦终止。结果 共有6例患者完成了爬坡试验,当试验进行到第1个剂量组时,出现2例DLT,试验终止。从而确定联合化疗方案的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO 12g／m²。主要不良反应为骨髓抑制,血小板减少的发生率为66.6％（4/6）,3级发生率为33.3％（2/6）;白细胞减少的发生率为83.3％（5/6）,未发生4级白细胞减少;中性粒细胞减少的发生率为83.3％（5/6）,4级发生率为33.3％（2/6）。所有患者经对症治疗后均好转,未影响继续治疗。结论 LBP联合ADM、IFO化疗方案新辅助治疗骨肉瘤的MTD为LBP 45mg／m²、ADM 60mg／m²和IFO12g／m²,毒副反应可耐受,建议以此为依据开展进一步临床研究。     

Hyperthermia enhances the cytotoxicity and platinum-DNA adduct formation of lobaplatin and oxaliplatin in cultured SW 1573 cells

The cytotoxicity of cisplatin and cisplatin-DNA adduct formation in vitro and in vivo is clearly enhanced by hyperthermia. We investigated whether cytotoxicity and platinum-DNA adduct formation of two promising new third-generation platinum derivatives, lobaplatin [1,2-diamminomethylcyclobutane platinum(II) lactate] and oxaliplatin [oxalato-1,2-diaminocyclohexane platinum(II)], are also enhanced by hyperthermia. Cisplatin was used for comparison. SW 1573 cells were incubated with cisplatin, lobaplatin or oxaliplatin at different concentrations for 1 h at 37°, 41° and 43°C. The reproductive capacity of cells was determined by cloning experiments. Immunocytochemical detection of platinum-DNA adducts was performed with the rabbit antiserum NKI-A59. At 37°C, cisplatin was the most cytotoxic, followed by oxaliplatin and lobaplatin. Hyperthermia clearly enhanced the cytotoxicity of cisplatin, lobaplatin and oxaliplatin. There was no further increase in cytotoxicity at 43°C compared to 41°C for cisplatin and oxaliplatin. A further increase in cytotoxicity at 43°C was observed for lobaplatin. At 43°C thermal enhancement was higher for lobaplatin than for oxaliplatin, with the reverse pattern at 41°C. For both drugs, thermal enhancement of cytotoxicity was lower than observed for cisplatin. Immunocytochemical detection of platinum-DNA adducts was feasible for all the drugs. Adduct formation was enhanced at 43°C for cisplatin, lobaplatin and oxaliplatin with a relative increase of 410%, 170% and 180%. These results seem to confirm that an increase in platinum-DNA adduct formation is involved in the in vitro thermal enhancement of cytotoxicity. The observed thermal enhancement of cytotoxicity of lobaplatin and oxaliplatin in vitro warrants further in vivo investigations.Abbreviation TER thermal enhancement ratio     

洛铂腹腔灌注联合替吉奥治疗晚期胃癌合并腹水的临床观察

目的 观察洛铂腹腔灌注联合替吉奥治疗晚期胃癌合并腹水的疗效和安全性.方法 依照入选标准,选择经病理学确诊的老年或体力状况较差的晚期胃癌伴腹水患者30例.治疗方案：经B超定位腹腔置管,尽量放尽腹水后,洛铂30 mg/m2腹腔灌注,第1天;替吉奥口服：体表面积（BSA）＜1.25 m2者,40 mg,2次/d;BSA 1.25～1.50 m2者,50 mg,2次/d;BSA≥1.50 m2者,60 mg,2次/d,连服14 d.21 d为1个周期,2个周期后评价疗效,观察有效率、疾病控制率、生活质量改善情况及毒副反应.结果 30例患者中完全缓解0例,部分缓解12例,稳定13例,进展5例,有效率为40.0％,疾病控制率为83.3％.12例患者经1～2周期化疗后腹水全部消失,8例患者腹水明显减少,10例无明显变化.主要毒副反应为骨髓抑制、胃肠道反应及疲乏,其中骨髓抑制以白细胞减少、血小板减少、贫血为主,胃肠道反应以恶心/呕吐、腹泻为主,大多为Ⅰ～Ⅱ级,Ⅲ级及以上白细胞减少、血小板减少分别占6.7％和3.3％,无严重肝、肾毒性及心脏毒性,无手足综合征,无腹膜反应,无治疗相关性死亡.结论 洛铂腹腔灌注联合替吉奥治疗老年或体力状况较差的合并腹水的晚期胃癌效果较高,毒性作用较小,可明显改善患者的生活质量.     

白蛋白结合型紫杉醇联合洛铂与顺铂治疗晚期非小细胞肺癌临床疗效比较

目的：旨在评价白蛋白结合型紫杉醇（Nab-paclitaxe,Nab-PC）联合洛铂与顺铂治疗晚期非小细胞肺癌（ⅢB和Ⅳ期）的临床疗效及毒副反应比较。方法：48例一线使用Nab-PC联合洛铂或联合顺铂治疗的晚期非小细胞肺癌（NSCLC）患者,分为治疗组和对照组,各24例患者。计算患者的近期缓解率（RR）、疾病控制率（DCR）、疾病进展时间（TTP）;观察患者的毒副反应及耐受性。结果：每例完成2~6个周期,共154个周期,平均每例完成3.2个周期,均可评价疗效。治疗组部分缓解10例（41.7%）,稳定10例（41.7%）,进展4例（16.6%）,RR 39.6%,DCR 81.3%;对照组部分缓解9例（37.5%）,稳定10例（41.7%）,进展5例（20.8%）,RR 37.5%,DCR 79.2%。两组数据无统计学差异。主要不良反应有血液学毒性、恶心呕吐、肾功能损害等;治疗组反应较对照组轻。结论：Nab-PC联合顺铂或洛铂方案是治疗晚期非小细胞肺癌安全有效方案之一,可以推荐在临床使用。