国产紫杉醇及长春瑞宾联合铂类治疗晚期非小细胞肺癌的临床对照研究

目的　探讨国产紫杉醇及长春瑞宾加顺铂及卡铂联合方案对晚期非小细胞肺癌 (NSCLC)的疗效和毒副反应。方法　选取初治晚期NSCLC 181例 ,分别应用NP(长春瑞宾 +顺铂 )、TC(国产紫杉醇 +卡铂 )及TP(国产紫杉醇 +顺铂 )方案治疗。每例均完成两周期化疗后评价疗效及毒副反应。结果　三组患者近期有效率分别为NP组 42 .4%,TC组 40 .3 %,TP组 43 .3 %,三组间有效率比较均无显著性差异 ( χ2 =0 .10 86,P >0 .0 5 )。NP组中位生存期为 8.4个月 ,TC组 9.4个月 ,TP组 8.9个月 (P >0 .0 5 )。NP组 1、2、3年生存率分别为 3 9.0 %、16.9%、5 .1%;TC组分别为 41.9%、2 1.0 %、6.5 %;TP组分别为 40 .0 %、18.3 %、5 .0 %,三组间比较无统计学差异 ( χ2 =0 .14 0 4,P >0 .0 5 )。三组毒副反应均以骨髓抑制、脱发及恶心呕吐为主 ,但均未影响治疗。三组病例均无化疗相关死亡发生。结论　NP、TC及TP联合方案是治疗晚期NSCLC有效且耐受性较好的方案     

Enhancement of Radiation Response by Paclitaxel in Mice According to Different Treatment Schedules

Purpose: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo.

Materials and methods: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD₅₀, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD₅₀, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed.

Results: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols.

Conclusions: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.     

In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active metabolite of irinotecan) in human carcinoma cell lines

Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects of drug combinations at the IC₈₀ level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic (subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist in determining the optimal schedule for this combination in clinical use. Received: 25 February 1997 / Accepted: 6 November 1997     

Potentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms-1 Cells

In the present study, we found that inostamycin increased the ability of paclitaxel to induce apoptosis in Ms-1 cells. A considerably higher concentration of paclitaxel was required for the induction of apoptosis in Ms-1 cells than in other cell lines tested. Treatment of Ms-1 cells with inostamycin, an inhibitor of phosphatidylinositol (PI) synthesis, reduced the dosage of paclitaxel required to induce cell death by apoptosis. This effect of inostamycin is specific to Ms-1 cells, and inostamycin did not increase the cytotoxicity of other antitumor drugs such as adriamycin, vinblastine, methotrexate, cisplatin, etoposide, or camptothecin in Ms-1 cells. Addition of inostamycin to paclitaxel-treated cells caused a significant increase in the sub G1 peak, representing apoptosis, which was accompanied by a decrease in the G2/M peak seen in paclitaxel-treated Ms-1 cells, without affecting paclitaxel-inhibited tubulin depolymerization. Moreover, paclitaxel did not enhance inostamycin-inhibited PI synthesis. The expression levels of Bcl-2, Bax, and Bcl-X_L were not changed following the co-treatment with inostamycin plus paclitaxel, whereas the activated form of caspase-3 was markedly increased. Thus, inostamycin is a chemosensitizer of paclitaxel in small cell lung carcinoma Ms-1 cells.     

RT-PCR检测乳腺癌患者外周血表皮生长因子受体和细胞角质蛋白-19mRNA的表达

目的　探讨逆转录聚合酶链式反应(RT-PCR )方法检测乳腺癌患者外周血表皮生长因子受体(EGFR)mRNA作为乳腺癌循环肿瘤细胞标志的可能性及意义。方法　以转录聚合酶链式反应(RT-PCR)方法,分别对40例乳腺癌患者和30例健康人静脉血进行EGFRmRNA检测,同时与目前研究较多的循环上皮细胞标志:细胞角质蛋白CK-19的mRNA做比较。结果　在30例健康人外周静脉血中没有发现EGFRmR NA的表达( 0% ),但有8例CK-19阳性( 26. 7% )。而40例乳腺癌患者检测出13例EGFRmRNA阳性(32. 5% ),与正常人相比P<0. 01,两组间存在显著性差异;CK-19的mRNA阳性例数为14 (35. 0% ),与正常人相比P>0. 05,两组间无统计学差异。通过免疫组化检测到25例( 62. 5% )的肿瘤组织中EGFR阳性,所有外周血中EGFRmRNA阳性的病例,相应的原发肿瘤病灶中EGFR蛋白均为阳性,组织中EGFR蛋白高表达的患者外周血EGFRmRNA检出率也高(P<0. 01)。26例初治患者中5例EGFRmRNA阳性(19. 2% ),14例复治患者中8例EGFRmRNA阳性(57. 1% ),两组相比P<0. 05,存在显著性差异。6例曾使用过紫杉醇类药物挽救化疗的转移性患者中1例EGFRmRNA阳性(16. 7% ), 8例未使用过紫杉醇类药物挽救化疗的转移性患者中7例EGFRmRNA阳性(87. 5% ),两组相比P<0. 05,存在显著性差异。结论　CK-19的     

放疗加紫杉醇治疗晚期鼻咽癌患者医院感染的临床分析

目的调查分析晚期鼻咽癌患者常规放疗同时行紫杉醇化疗过程中并发医院感染及相关因素,探讨有效的防治措施。方法对我院26例行放疗同时紫杉醇化疗鼻咽癌住院患者发生医院感染及危险因素进行回顾性分析。结果26例住院患者发生医院感染20例,占76.9%;检出致病菌26株,其中以白色念珠菌为主,占46.2%,革兰阴性菌占38.5%,革兰阳性菌占11.5%;鼻咽癌放疗、化疗同步治疗并发医院感染与长期住院、口腔黏膜损伤、白细胞下降、不合理应用抗生素和糖皮质激素等因素有关。结论缩短平均住院日、加强口腔护理、预防白细胞下降、合理应用抗生素和糖皮质激素,以减少鼻咽癌同步放化疗患者医院感染的发生率。     

以国产紫杉醇为主的方案治疗转移性乳腺癌

目的评价以国产紫杉醇为主的方案治疗转移性乳腺癌的近期疗效和不良反应。方法12例乳腺癌根治术后患者发生一处或多处转移,均有可评价客观指标,采用紫杉醇+表阿霉素方案或紫杉醇+顺铂方案化疗。具体为紫杉醇135mg/m2,第1天,静脉滴注3小时;表阿毒素60mg/m2第1天静脉推注或分2天静脉推注;顺铂80mg/m2分3天静脉滴注,并适量水化、利尿等。紫杉醇使用前12小时、6小时分别口服地塞米松20mg,且给药前30分钟予非那根25mg肌肉注射和西米替丁400mg静脉推注。表阿霉素在紫杉醇前使用,顺铂在紫杉醇后使用。结果本组12例CR1例、PR5例、NC2例、PD4例,总有效率50%。主要不良反应为骨髓抑制和脱发,其次为消化道反应和肌肉关节酸痛。结论以国产紫杉醇为主的方案治疗转移性乳腺癌有效率较高,不良反应可耐受。     

紫杉醇与铂类药物联合治疗进展期非小细胞肺癌的临床观察

目的 观察紫杉醇加顺铂或卡铂治疗进展期非小细胞肺癌的疗效与毒副反应。方法 采用紫杉醇加顺铂（或卡铂）方案治疗32例进展期非小细胞肺癌患者，观察近期疗效和毒副反应。结果 完全缓解（CR）2例，部分缓解（PR）13例，疾病稳定（SD）11例，疾病进展（PD）6例，总有效率（CR＋PR）为：46．9％。主要毒副反应是脱发，粒细胞减少，贫血，胃肠道反应等。结论 紫杉醇联合顺铂（或卡铂）治疗进展期非小细胞肺癌疗效肯定，毒副反应可以耐受。     

回顾性对紫杉醇两种药物在我院临床抗肿瘤治疗应用的前景探讨

目的:对紫杉醇国产与进口药物在肿瘤治疗中的应用情况及药物经济学进行分析和评估.方法:采用回顾性调查方法随机抽查,应用国产和进口紫杉醇的肿瘤患者各15例,进行数据的搜集及整理,分析用量、疗效、副作用及单品种治疗费用.结果:经过探讨初步认定,国产紫杉醇疗效、副作用与进口紫杉醇差异小且价格低,在一定程度上减轻病人负担,国产紫杉醇药品单药治疗费用平均为22785.75元,而进口紫杉醇药品单药治疗费用平均56570.67元.结论:国产与进口紫杉醇在治疗乳腺癌、肺癌、胃癌、卵巢癌的临床疗效均无显著性差异,但品种治疗费用明显降低.     

紫杉醇联合CF／5-FU治疗晚期胃癌22例临床观察

目的 观察紫杉醇为主联合亚叶酸钙／5-氟尿嘧啶（5-FU）治疗晚期胃癌的疗效及不良反应。方法 化疗方案：紫杉醇（Taxol）＋亚叶酸钙（CF）／5-FU，28d为一个周期，连用2周期后评价疗效。Taxol每周疗法，60mg／m^2加入0．9％生理盐水500mL静滴，不少于3h，d1、d8、d15；CF200mg，d1-d5，5-FU 600mg／m^2，d1-5。结果 全组共完成化疗70周期，22例均可评价疗效，全组1例CR（4．6％），8例PR（36．4％），总有效率40．9％。8例SD（36．4％）；5例PD（22．7％）。毒副作用，主要为骨髓抑制，白细胞减少占81．8％，其中Ⅰ、Ⅱ级占77．3％；脱发占81．8％，均为Ⅰ、Ⅱ级；肌肉节痛占54．5％；其它还包括过敏（4．6％）、腹泻（9．1％）、肝功异常（22．8％）、心电图异常（4．6％）等。但无严重超敏反应，无治疗相关性死亡。结论 晚期胃癌病人使用以紫杉醇为主联合化疗方案具有一定的疗效，毒副反应可以耐受，在晚期胃癌缺乏有效治疗措施的情况下可作为一种较好选择。