后程适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期非小细胞肺癌

目的　观察三维适形放射治疗联合长春瑞滨（ＮＶＢ）加顺铂（ＤＤＰ）同步化疗治疗Ⅲ期非小细胞肺癌（ＮＳＣＬＣ）的疗效及耐受性。方法　５０例Ⅲ期ＮＳＣＬＣ患者随机分为同步放化疗组和单放组,每组各２５例。单放组采用６ＭＶ或１５ＭＶＸ线常规外放疗ＤＴ４０Ｇｙ,后采用三维适形放疗２.５～３Ｇｙ／ｆ,１ｆ／ｄ,至ＤＴ７０～７５Ｇｙ,同步放化疗组在放疗的第１～３天联合ＮＰ方案化疗（ＮＶＢ２５ｍｇ／ｍ^２,ｄ_１、ｄ_８,ＤＤＰ３０ｍｇ／ｍ^２,ｄ_１～ｄ_３）,２１天为１周期,放疗后再采用该方案化疗３～６个周期。结果　同步放化疗组与单放组的有效率（ＣＲ＋ＰＲ）分别为８４.０％和６４.０％（Ｐ＞０.０５）;１、２年生存率分别为７６.０％、３６.０％和６８.０％、２４.０％（Ｐ均＞０.０５）。主要毒副反应表现为骨髓抑制和消化道反应。结论　后程三维适形放射治疗联合ＮＰ方案同步化疗治疗Ⅲ期ＮＳＣＬＣ近期疗效好,且毒性反应可以耐受。     

羟基喜树碱联合奥沙利铂、氟尿嘧啶和亚叶酸钙治疗晚期胃癌的临床研究

目的　观察羟基喜树碱（ＨＣＰＴ）联合奥沙利铂（ＯＸＡ）、氟尿嘧啶（５ ＦＵ）及亚叶酸钙（ＣＦ）联合治疗晚期胃癌的近期疗效及毒副反应。方法　ＨＣＰＴ１０ｍｇ／ｍ^２静脉滴注,ｄ_１～ｄ_５;ＯＸＡ１００ｍｇ／ｍ^２静脉滴注,ｄ_１;５-ＦＵ７５０ｍｇ／ｍ^２静脉滴注,ｄ_６～ｄ_１０;ＣＦ１００ｍｇ／ｍ^２静脉滴注,ｄ_６～ｄ_１０。每２８天为１个周期,连续２个周期后评价疗效。结果　５４例均可评价疗效,ＣＲ４例,ＰＲ２７例,有效率为５７.４％,中位疾病进展时间（ＴＴＰ）为４.５个月,中位总生存时间（ＯＳ）８个月。主要毒副反应为白细胞减少、血红蛋白减少、胃肠道反应和脱发。结论　ＨＣＰＴ联合ＯＸＡ、５-ＦＵ、ＣＦ治疗晚期胃癌有较好的疗效,且毒性可以耐受,值得进一步研究。     

ＮＰ方案与ＤＰ方案同期放化疗治疗局部晚期非小细胞肺癌的比较

目的　比较ＮＰ方案和ＤＰ方案进行同期放化疗治疗局部晚期非小细胞肺癌（ＮＳＣＬＣ）的临床疗效和毒性反应。方法　８２例不能手术的ⅢＡ期及ⅢＢ期ＮＳＣＬＣ患者（ⅢＡ２６例,ⅢＢ５６例）根据入选标准随机分组,其中４０例进入ＮＰ组,４２例进入ＤＰ组。ＮＰ组：化疗方案：长春瑞滨（ＮＶＢ）１５～１８ｍｇ／ｍ^２ｄ_１,ｄ_８;顺铂（ＤＤＰ）７０ｍｇ／ｍ^２ｄ_１。放射治疗从第１天开始,６ＭＶ-Ｘ射线照射,三维适形照射ＤＴ４０Ｇｙ／４～４.５ｗ后缩野,追加剂量至ＤＴ６０～６５Ｇｙ／６～６.５ｗ。ＤＰ组：化疗方案：多西紫杉醇（ＤＯＣ）７０～７５ｍｇ／ｍ^２ ｄ_１,ＤＤＰ７０ｍｇ／ｍ^２ ｄ_１,放射治疗方案同ＮＰ组。结果　所有患者均顺利完成治疗。ＮＰ组获ＣＲ１０.０％,ＰＲ５２.５％,ＳＤ２５％,ＰＤ１９.１％;ＤＰ组获ＣＲ１１.９％,ＰＲ５.８％,ＳＤ２3.８％,ＰＤ９.５％,两组近期疗效差异无统计学意义（Ｐ＞０.０５）。两组患者的ＣＥＡ、ＣＹＦＲＡ２１ １和ＣＡ１９ ９治疗后均比治疗前有降低,但两组之间差异无统计学意义（Ｐ＞０.０５）。ＮＰ组和ＤＰ组的１年、２年和３年生存率分别为６５％、４２.５％、３７.５％和７６.２％、５７.１％、４５.２％。ＮＰ组和ＤＰ组的１年、２年和３年局部控制率分别为６８.９％、４８.９％、４２.２％和７９.１％、６５.１％、５１.２％。主要毒副反应为放射性食管炎和白细胞减少,两组患者的１～３级放射性食管炎和２～４级白细胞减少发生率均较高。结论　ＮＰ为化疗方案的同期放化疗和ＤＰ为化疗方案的同期放化疗疗效没有明显差异,毒副反应也相似。     

洛铂联合氟尿嘧啶治疗晚期食管癌的临床观察

目的　观察洛铂联合氟尿嘧啶（５-ＦＵ）治疗晚期食管癌的疗效和毒副作用。方法　２００９年８月至２０１０年３月,将４８例晚期食管癌患者分为观察组（ｎ＝２６）和对照组（ｎ＝２２）。观察组：洛铂３０ｍｇ／ｍ^２ 静滴,ｄ_１;亚叶酸钙２００ｍｇ／ｍ^２ 静滴,ｄ_１～ｄ_５;５-ＦＵ５００ｍｇ／ｍ^２静滴,ｄ_１～ｄ_５。对照组：顺铂２０ｍｇ／ｍ^２静滴,ｄ_１～ｄ_４;亚叶酸钙２００ｍｇ／ｍ^２静滴,ｄ_１～ｄ_５;５-ＦＵ５００ｍｇ／ｍ^２静滴,ｄ_１～ｄ_５。两组化疗均２１天为１周期。比较两组的疗效、不良反应以及生存随访情况。结果　４８例患者均可评价疗效,其中观察组的有效率为５３.８％,对照组为５０.０％,两组差异无统计学意义（Ｐ＞０.０５）。两组主要不良反应为消化道反应和骨髓抑制,其中观察组的恶心呕吐发生率低于对照组（Ｐ＜０.０５）,血小板减少发生率高于对照组（Ｐ＜０.０５）。观察组和对照组的中位疾病进展时间分别为３.７个月和３.４个月,中位生存期分别为８.７个月和８.２个月。结论　洛铂联合氟尿嘧啶治疗晚期食管癌的疗效较好,毒副反应可以耐受,值得临床进一步研究应用。     

吉西他滨联合氟尿嘧啶类药物治疗耐药性晚期结直肠癌的临床观察

目的　观察吉西他滨（ＧＥＭ）联合氟尿嘧啶类药物治疗耐药性晚期结直肠癌（ｍＣＲＣ）的有效性和安全性。方法　３２例二线及二线以上方案化疗失败的ｍＣＲＣ患者,使用ＧＥＭ（１０００ｍｇ／ｍ^２,ｄ_１、ｄ_８）联合氟尿嘧啶（５-ＦＵ５００ｍｇ／ｍ^２,ｄ_１～ｄ_５）１３例,联合卡培他滨（１２５０ｍｇ／ｍ^２,ｄ_１～ｄ_１４）１９例,直至疾病进展或出现不可耐受的不良反应,每２个周期按照ＲＥＣＩＳＴ标准（１.０版）进行疗效评价,按ＮＣＩ-ＣＴＣ（３.０版）评价毒性并随访生存情况。结果　３２例均可评价疗效和毒性,其中获ＰＲ４例,ＳＤ１４例,ＰＤ１４例,疾病控制率（ＤＣＲ）为５６.３％,中位肿瘤进展时间（ｍＴＴＰ）为３.８个月,中位总生存时间（ｍＯＳ）为８.１个月。主要毒副反应为骨髓抑制、皮疹及发热,多为１～２级,支持对症处理可以恢复。结论　ＧＥＭ联合氟尿嘧啶类药物治疗国人耐药性ｍＣＲＣ具有一定疗效,不良反应可以耐受,值得进一步研究。     

培美曲塞联合低剂量ＦＰ方案治疗难治性晚期胃癌的临床观察

目的　观察培美曲塞联合低剂量ＦＰ方案在晚期难治性胃癌的疗效和不良反应。方法　全组２５例患者应用培美曲塞联合低剂量ＦＰ方案化疗,具体方法：培美曲塞５００ｍｇ／ｍ^２ｄ_１;低剂量ＦＰ方案：氟尿嘧啶（５-ＦＵ）２５０ｍｇ／ｍ^２化疗泵静脉持续静滴,ｄ_１～ｄ_１４;顺铂（ＤＤＰ）６ｍｇ／ｍ^２,ｄ_１～ｄ_５、ｄ_８～ｄ_１２。每３周为１周期,平均用药３.个周期。结果　２５例患者均可评价疗效,其中ＰＲ８例,ＳＤ１３例,ＰＤ４例,总有效率３２％（８／２５）。中位随访８.个月（２.～２４个月）,中位无肿瘤进展时间为４.个月（９５％ＣＩ：３.～７.个月）,中位总生存时间７.个月（９５％ＣＩ：６.～１３.个月）。主要不良反应为骨髓抑制和黏膜炎。结论　培美曲塞联合低剂量ＦＰ方案对难治性晚期胃癌患者疗效较好,不良反应可以耐受,值得深入研究。     

晚期胃癌一线化疗失败后不同解救化疗方案的疗效比较

目的　回顾性分析不同化疗方案对一线化疗失败的晚期胃癌患者进行解救治疗的疗效和安全性,探讨晚期胃癌二线治疗适宜的化疗方案。方法　８８例一线化疗失败的晚期胃癌患者,分为紫杉类组（３２例）：多西紫杉醇６０～７５ｍｇ／ｍ^２或紫杉醇１３５～１７５ｍｇ／ｍ^２,分ｄ_１、ｄ_８;５-ＦＵ５００ｍｇ／ｍ^２ｄ_１～ｄ_５或顺铂２０ｍｇｄ_１～ｄ_５,２１天为１周期。奥沙利铂组（３１例）：奥沙利铂８５ｍｇ／ｍ^２ｄ_１;５-ＦＵ４００ｍｇ／ｍ^２ｉｖｄ_１、ｄ_２,５-ＦＵ６００ｍｇ／ｍ^２,ｃｉｖ２２ｈ,ｄ_１、ｄ_２;ＣＦ２００ｍｇ／ｍ^２ｄ_１、ｄ_２,１４天为１周期。伊立替康组（２５例）：伊立替康１５０～１８０ｍｇ／ｍ^２,ｄ_１;５-ＦＵ４００ｍｇ／ｍ^２ｉｖｄ_１、ｄ_２,５-ＦＵ６００ｍｇ／ｍ^２,ｃｉｖ２２ｈ,ｄ_１、ｄ_２;ＣＦ２００ｍｇ／ｍ^２ｄ_１、ｄ_２,１４天为１周期。结果　８８例均可评价不良反应,８２例可评价客观疗效。紫杉类组、奥沙利铂组以及伊立替康组总有效率分别为３.２％、１４.３％和１７.４％,疾病控制率分别为４８.４％、６０.７％和６５.２％;中位ＰＦＳ分别为２个月（１.３９～２.６１个月）、３个月（２.１６～３.８４个月）和３个月（２.４６～３.５４个月）,差异无统计学意义（Ｐ＝０.１９５）;中位ＯＳ为６个月（４.２１～７.７９个月）、７个月（６.１２～７.８８个月）和７个月（５.０８～８.９２个月）,差异无统计学意义（Ｐ＝０.３９３）。３组不良反应易耐受,主要为１～２级血液学毒性。伊立替康组腹泻发生率较高,为４８％,但３级以上发生率较低,仅为８％。奥沙利铂组外周神经毒性为４８％。结论　晚期胃癌一线治疗失败后采用目前常用的化疗方案解救治疗有一定的客观缓解率和临床受益率,但疗效有限,需要进一步积极探索有效的治疗方案。     

局部晚期鼻咽癌放疗同步ＰＦ方案或顺铂单药的临床对照研究

目的　对比观察顺铂（ＤＤＰ）单药用于局部晚期鼻咽癌同步放化疗与ＤＤＰ联合氟尿嘧啶（５-ＦＵ）方案（ＰＦ方案）同步放化疗的有效性和安全性。方法　７６例局部晚期鼻咽癌分为两组,４０例接受ＰＦ方案同步放化疗（５-ＦＵ５００ｍｇ／ｍ^２静滴,ｄ１～ｄ５;ＤＤＰ８０ｍｇ／ｍ^２静滴,ｄ１,２１天为１周期）,３６例接受ＤＤＰ单药同步放化疗（ＤＤＰ４０ｍｇ／ｍ２静滴,每周１次,共７次）。鼻咽部病灶及颈部阳性淋巴结给予放疗总量为７０Ｇｙ,颈部预防性照射给予放疗量５０Ｇｙ。结果　全部患者均可评价疗效和毒副反应,ＰＦ方案组及ＤＤＰ单药组有效率均为１００％。ＰＦ方案组的１、３年生存率分别为１００％、８５％,ＤＤＰ单药组分别为１００％、８９％（Ｐ＞０.０５）;ＰＦ方案组与ＤＤＰ单药组的３年无进展生存率分别为７７.５％和７５.０％ （Ｐ＞０.０５）;ＰＦ方案组的中位生存时间为５０.６个月,ＤＤＰ单药组为４８.０个月（Ｐ＞０.０５）。两组毒副反应以恶心呕吐、口腔黏膜炎及白细胞减少为主,差异均有统计学意义（Ｐ＜０.０５）。结论　ＤＤＰ单药与ＰＦ方案用于局部晚期鼻咽癌同步放化疗的疗效相近,患者均可耐受,但ＤＤＰ单药组反应较轻。     

周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌的临床观察

目的　观察周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌的疗效和安全性。方法　２８例经顺铂加氟尿嘧啶方案一线化疗失败的晚期食管癌患者,应用多西紫杉醇２５ｍｇ／ｍ^２,静脉滴注１ｈ,ｄ_１、ｄ_８、ｄ_１５,卡培他滨（希罗达）１５００ｍｇ／ｍ^２,分每日２次口服,ｄ_１～ｄ_１４,２８天为１周期。结果　２８例患者中２６例可评价疗效,获ＣＲ１例,ＰＲ１０例,ＳＤ８例,ＰＤ７例,总有效率（ＣＲ＋ＰＲ）为３９.３％。所有患者中位疾病进展时间（ＴＴＰ）为４.２个月（９５％ＣＩ：１.６～６.０个月）,中位生存时间（ＯＳ）为７.８个月（９５％ＣＩ：６.３～９.３个月）。主要毒副反应为骨髓抑制,出现３～４级中性粒细胞减少１２例（４２.９％）,３级贫血５例（１７.９％）,３级血小板减少３例（１０.７％）,无治疗相关性死亡。结论　周剂量多西紫杉醇联合卡培他滨二线治疗晚期食管癌有一定疗效,患者耐受性较好,值得临床进一步研究。     

肺耐药蛋白基因表达与紫杉醇脂质体联合顺铂治疗非小细胞肺癌疗效关系的探讨

目的　探讨肺耐药蛋白基因（ＬＲＰ）在非小细胞肺癌（ＮＳＣＬＣ）中的表达与化疗疗效之间的关系。方法　采用免疫组织化学Ｓ Ｐ法对４７例ＮＳＣＬＣ经气管镜活检组织进行ＬＲＰ表达水平的检测;采用ＴＰ方案化疗：紫杉醇脂质体１３５ｍｇ／ｍ^２,ｄ_１、ｄ_８,顺铂８０ｍｇ／ｍ^２,ｄ_１,３周为１周期,化疗２周期后评价疗效。结果　ＮＳＣＬＣ中ＬＲＰ的表达阳性率为６１.７０％,在肺腺癌和肺鳞癌中的表达阳性率分别为７６.９２％和４２.８６％（Ｐ＜０.０５）,ＬＲＰ表达水平与ＴＮＭ分期无关（Ｐ＞０.０５）。ＴＰ方案化疗２个周期后总有效率为４２.５５％,其中ＬＲＰ表达阳性和阴性的有效率分别为２７.５９％和６６.６７％（Ｐ＜０.０１）。结论　ＬＲＰ在ＮＳＣＬＣ中存在不同程度的表达,其表达在肺腺癌和肺鳞癌之间有差异,并与ＴＰ方案化疗的近期疗效相关。     

吉西他滨联合顺铂方案与多西他赛联合奈达铂方案对晚期肺鳞癌的疗效比较

目的 比较吉西他滨+顺铂方案及多西他赛+奈达铂方案治疗晚期肺鳞癌患者的疗效及安全性.方法 选取晚期肺鳞癌患者60例作为研究对象,分别采用吉西他滨+顺铂方案(GP)及多西他赛+奈达铂方案(TN)化疗,比较其治疗效果、生存期、不良反应.结果 GP组患者PR患者4例,SD患者8例,PD患者18例,总有效率为40.00％,TN组总有效率30％,差异有统计学意义(P ＜0.05);GP组6个月生存28例,占93.33％,1年生存率为76.67％,2年生存率为50.00％,均明显高于TN组,差异有统计学意义(P＜0.05);GP组WBC减少占40.00％,PLT减少占30.00％,均高于TN组,末梢神经毒性、脱发发生率均低于TN组,差异有统计学意义(P＜0.05);在恶心呕吐、贫血、肝毒性、肾毒性等方面两组比较差异无统计学意义(P＞0.05).结论 对晚期肺鳞癌患者采用吉西他滨联合顺铂方案、多西他赛联合奈达铂方案化疗,均能取得较高的治疗效果,吉西他滨联合顺铂方案化疗能更好的延长晚期肺鳞癌患者生存期方面均有一定的优势,不良反应可耐受,安全性较好.     

替吉奥联合奈达铂对比多西他赛单药二线治疗晚期肺鳞癌的疗效观察

目的 探讨替吉奥（S-1）联合奈达铂与多西他赛单药二线治疗晚期肺鳞癌的疗效和安全性。方法 收集本院2012年12月至2014年12月一线含铂双药化疗方案治疗失败或缓解后再进展的晚期肺鳞癌患者共87例,其中43例接受S-1联合奈达铂治疗（观察组）,44例接受多西他赛单药治疗（对照组）,两方案均为21天1个周期。化疗2个周期后采用RECIST 1.1 版标准评价客观疗效,采用美国国立癌症研究所毒性判定标准（NCI-CTCAE）4.0评价毒性反应,同时随访生存情况并评价两组生活质量的改善程度。结果 87例患者均可评价疗效。观察组和对照组的有效率分别为23.3％和18.2％,差异无统计学意义（P＞0.05）;观察组的疾病控制率为65.1％,高于对照组的40.9％,差异有统计学意义（P＜0.05）;两组中位无疾病进展生存期分别为3.6个月（95%CI：2.44～4.76个月）和2.9个月（95%CI：2.54～3.26个月）,差异有统计学意义（P＜0.05）;两组治疗后生活质量均有相应改善,差异无统计学意义（P＞0.05）。观察组主要的毒副反应为血液学毒性和消化道反应,对照组主要的毒副反应为血液学毒性和口腔黏膜炎,两组不良反应经对症治疗均可缓解。结论 S-1联合奈达铂二线治疗晚期肺鳞癌疗效更佳,不良反应可耐受。     

A single-institute phase I/II trial combining nedaplatin dose escalation with a fixed dose of docetaxel for induction chemotherapy of oral squamous cell carcinoma

The purpose of this clinical trial was to assess the toxicity and efficacy of docetaxel plus nedaplatin induction chemotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). Twenty-one patients were enrolled in this phase I/II clinical study. The toxicities, response rates, and the maximum tolerated dose of nedaplatin that could be safely given preoperatively were assessed. Patients received escalating doses of nedaplatin (60, 70, 80, 90 mg/m²) combined with a fixed dose of docetaxel (60 mg/m²) on day one. Dose-limiting toxicity (DLT), grade 4 leukopenia lasting for two days or more, was seen in one patient at dose level 3; no other DLT was observed at any dose level. The overall response rate was 66.7%. The response rate was 100% at nedaplatin dose level 4, while that at dose level 1 was low (33.3%). Given these results, the recommended dose of nedaplatin in this regimen combined with fixed dose docetaxel (60 mg/m²) was determined to be 90 mg/m². Docetaxel 60 mg/m² plus nedaplatin 90 mg/m² induction chemotherapy can be recommended for patients with locally advanced oral squamous cell carcinoma. Based on these results, an early phase II clinical study using this dose level was conducted; docetaxel plus nedaplatin induction chemotherapy appears to be a useful regimen for the treatment of OSCC. A late phase II clinical study is warranted.     

奈达铂联合多西紫杉醇治疗晚期非小细胞肺癌的临床观察

目的探讨奈达铂联合多西紫杉醇治疗晚期非小细胞肺癌的疗效和毒性。方法对23例晚期非小细胞肺癌应用奈达铂联合多西紫杉醇治疗,并对其疗效及毒性进行分析。结果奈达铂联合多西紫杉醇治疗晚期非小细胞肺癌的总有效率为39.3%,其中鳞癌有效率为38.5%,腺癌有效率为40.0%,主要不良反应为骨髓抑制、恶心、呕吐,绝大多数患者耐受性良好。结论奈达铂联合多西紫杉醇治疗晚期非小细胞肺癌安全,有效,值得临床推广应用。     

奈达铂为基础化疗联合同步放疗治疗II-III期食管鳞状细胞癌的疗效观察

目的:探索在II-III期食管鳞癌同步放化疗中多西他赛联合奈达铂方案、S-1联合奈达铂方案与单药奈达铂化疗的疗效和安全性。方法:回归性纳入2016年1月至2017年1月就诊于我院的106例行同步放化疗的II-III期食管鳞癌患者。所有患者根据化疗方案分为三组,分别为:S-1联合奈达铂治疗组、多西他赛联合奈达铂治疗组和奈达铂单药治疗组。通过电子病历系统及随访获取患者相关信息,比较三种不同化疗方案疗效和安全性。结果:106例患者中41例为S-1联合奈达铂化疗、45例接受多西他赛联合奈达铂化疗、20例为单药奈达铂化疗。总体ORR为79.25%,三组不同化疗方案患者在CR、PR、SD、PD和ORR方面均无显著统计学差异。患者中位OS和PFS分别为25.3月和17.1月,三组患者在OS和PFS之间均无显著性差异。多西他赛联合奈达铂患者3度以上白细胞减少发生率显著高于S-1联合奈达铂和奈达铂单药（29/45 vs 12/41 vs 6/20,P=0.002）,S-1联合奈达铂患者腹泻发生率显著高于多西他赛联合奈达铂和奈达铂单药组（8/41 vs 3/45 vs 0/20,P=0.031）。结论:奈达铂为基础化疗联合同步放疗是II-III期食管鳞癌的有效治疗方法,多西他赛联合奈达铂、S-1联合奈达铂化疗和奈达铂单药化疗之间疗效接近,但S-1联合奈达铂化疗和奈达铂单药化疗不良反应优于多西他赛联合奈达铂化疗。     

培美曲塞二钠联合奈达铂治疗晚期肺腺癌的临床研究

目的:观察培美曲塞二钠(PEM)及多西他赛(DTX)分别联合奈达铂(NDP)治疗晚期肺腺癌的临床疗效及不良反应.方法:共收集225例经病理和(或)细胞学确诊的中晚期肺腺癌患者,随机分为培美曲塞组(109例)和DTX组(116例).培美曲塞组采用PEM和NDP方案联合化疗,PEM 500 mg/m2,静脉滴入,d1;NDP 80 mg/m2,静脉滴入,d1,21 d为1个周期;DTX组采用DTX和NDP方案联合化疗,DTX 75 mg/m2,静脉滴入,d1;NDP 80 mg/m2,静脉滴入,d1,21d为1个周期.结果:培美曲赛组治疗有效率及控制率均比DTX组高,差异有统计学意义(x2=2.35,P=0.041;x2=4.23,P=0.033).培美曲赛组与DTX组不良反应两组间相比较差异均无统计学意义.其中不良反应发生率较高的是血红蛋白下降、白细胞下降和血小板下降,而肝肾功能损害较为少见,恶心、呕吐和食欲不振的发生率较低.结论:PEM联合NDP方案治疗晚期肺腺癌患者疗效好,不良反应较轻,患者耐受性好,值得在临床进一步推广验证.     

Phase II study of nedaplatin and docetaxel in patients with advanced squamous cell carcinoma of the lung

BackgroundThe treatment of squamous cell carcinoma of the lung has not advanced sufficiently. Nedaplatin is a second-generation platinum compound that is active against squamous cell carcinoma of the lung, with a response rate of ∼40%.Patients and methodsEligible patients with advanced squamous cell carcinoma of the lung were treated with docetaxel (60 mg/m²) and nedaplatin (100 mg/m²) administered i.v. on day 1; these doses were determined in an earlier phase I study. The treatment cycles were repeated every 3 weeks. The primary end point was the response rate, and the secondary end points were overall survival, progression-free survival, and toxicity.ResultsTwenty-one patients were enrolled. Eighteen of the patients were male, and the median age was 67 years. The objective response rate was 62%. The median progression-free survival time was 7.4 months. The median survival time was 16.1 months, and the 1-year survival rate was 66.7% (95% confidence interval 46.5% to 86.8%). The most common adverse event was neutropenia (grade 3/4, 86%). Non-hematological toxic effects were relatively mild. One patient died of sepsis.ConclusionsCombination chemotherapy with nedaplatin and docetaxel is highly active and has an acceptable toxicity. Further investigation of nedaplatin and docetaxel is warranted.     

Differential efficacy of docetaxel according to non-small cell lung cancer histology and the therapeutic effect of epidermal growth factor receptor tyrosine kinase inhibitors

The active mutation of epidermal growth factor receptor (EGFR) and clinical characteristics are significant biomarkers for chemotherapy selection in non-small cell lung cancer (NSCLC). Although docetaxel is a key agent in second-line therapy for NSCLC, predictive biomarkers for assessing its efficacy have yet to be determined. To assess the clinical efficacy of docetaxel in second-line therapy for NSCLC according to NSCLC histology and the therapeutic effect of EGFR-tyrosine kinase inhibitors (EGFR-TKIs), we retrospectively reviewed 454 NSCLC patients treated with docetaxel between April 2002 and April 2009. In total, 239 patients with advanced NSCLC treated with docetaxel as second-line therapy following failure of platinum-based chemotherapy were analyzed in this study. A total of 59 (25%) patients had squamous cell carcinoma. The overall response rate and median progression-free survival time in the squamous cell group were significantly inferior to those in the non-squamous cell group (p=0.031 and p=0.005, respectively). Following the failure of docetaxel, 91 non-squamous patients were treated with EGFR-TKIs. The patients that achieved clinical benefit from EGFR-TKIs (n=32) demonstrated a significantly better response rate and longer progression-free survival compared to the other group (p<0.001 and p=0.027, respectively). In the univariate and multivariate analysis, the favorable therapeutic effect of EGFR-TKIs had an independent effect on progression- free survival (HR 1.484, p=0.0464). In conclusion, this retrospective study suggests that non-squamous histology and favorable therapeutic effect from EGFR-TKIs are useful markers for predicting the efficacy of docetaxel in second-line therapy for NSCLC.     

微血管密度和细胞凋亡在多西他赛增敏加3D-CRT治疗局部晚期非小细胞肺鳞癌中的表达

目的：观察单药多西他赛周疗联合3D-CRT同步对局部晚期非小细胞肺鳞癌AI、MVD的影响,MVD、AI与T0.5三者间的相关性,探讨多西他赛放疗增敏的分子生物学机制.方法：60例均经病理证实为鳞癌的初治病人入组,临床分期Ⅲa-Ⅲb.随机分为两组,观察组：（3D-CRT＋多西他赛增敏＋辅助化疗）30例,从放疗第1天开始,多西他赛静脉滴注（36mg/m2）,每周1次,共6周,放疗结束后TP方案化疗4周期;对照组（3D-CRT＋辅助化疗）30例,放疗结束后TP方案化疗4-6周期.放疗前及放疗（20Gy）后的24小时内,各行支气管镜活检1次,两次取材部位相同.采用免疫组化染色SP法对肿瘤标本进行微血管密度（MVD）检测,TUNEL法检测肺癌细胞凋亡标记指数（AI）,计算肿瘤缩小50％所需的时间（T0.5）.结果：观察组MVD表达降低较对照组有明显差异（P＜0.05）,观察组治疗前后诱导AI增加较对照组有明显差异（P＜0.05）,MVD表达降低与T0.5呈负相关（r=-0.624,P＜0.05）,AI表达增加与T0.5没有相关性.结论：多西他赛有可能通过降低MVD表达、诱导AI增加达到放疗增敏的目的,单药多西他赛周疗联合3D-CRT可有效改善局部晚期非小细胞肺鳞癌患者的预后,从而提高病人的生活质量.     

A retrospective study of second-line chemotherapy for unresectable or recurrent squamous cell carcinoma of the esophagus refractory to chemotherapy with 5-fluorouracil plus platinum

Background In Japan, chemotherapeutic agents that have been approved for the treatment of esophageal cancer include cisplatin, nedaplatin, 5-fluorouracil, vindesine, and docetaxel. We retrospectively investigated the efficacy and toxicity of a combination of nedaplatin plus vindesine, or docetaxel alone, for patients with unresectable or recurrent squamous cell carcinoma of the esophagus refractory to prior chemotherapy with 5-fluorouracil plus platinum. Methods Nedaplatin was administered at 90 mg/m² intravenously on day 1, and vindesine was administered at 3 mg/m² intravenously on days 1 and 8 every 28 days. Docetaxel 60 mg/m² or 70 mg/m² was administered intravenously every 21 days. We analyzed the response rate, overall survival time, progression-free survival time, and toxicity in 24 patients treated with nedaplatin plus vindesine and 28 patients treated with docetaxel. Results In patients treated with nedaplatin plus vindesine, the response rate of the 13 patients with measurable lesions was 8% (1/13), the median progression-free survival time was 1.8 months, and the median survival time was 5.5 months. In patients treated with docetaxel, the response rate of the 17 patients with measurable lesions was 18% (3/17), the median progression-free survival time was 2.1 months, and the median survival time was 5.1 months. The most frequent toxicity was neutropenia (grade 4; 13% in the group with nedaplatin plus vindesine and 50% in the docetaxel group), and febrile neutropenia (grade 3; 4% and 18%, respectively). Conclusion The efficacy of the two regimens for unresectable or recurrent squamous cell carcinoma of the esophagus refractory to chemotherapy with 5-fluorouracil plus platinum was unsatisfactory. New, more effective therapies are needed.