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。     

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。     

洛铂联合５-ＦＵ／ＣＦ治疗晚期胃、结直肠癌的剂量爬坡试验

目的　观察国人对不同剂量洛铂联合５-ＦＵ／ＣＦ治疗晚期胃、结直肠癌的耐受性、毒性反应以及与剂量的关系,探讨洛铂在联合化疗中的人体安全耐受剂量。方法　选取洛铂从低剂量逐渐至高剂量,５-ＦＵ和ＣＦ剂量不变,每剂量组至少３例受试者。初始剂量为洛铂２５ｍｇ／ｍ^２ｄ_１,５-ＦＵ４００ｍｇ／ｍ^２ｄ_１～ｄ_５,ＣＦ２００ｍｇ／ｍ^２ｄ_１～ｄ_５,２１ｄ为１周期;如无明显毒性反应则进入下一剂量组,直至最大耐受量（ＭＴＤ）或５０ｍｇ／ｍ^２。结果　１８例晚期胃、结直肠癌患者进入试验,分别进行了６个剂量组的研究,最高剂量组为５０ｍｇ／ｍ２,未观察到ＭＴＤ。主要毒性反应为血红蛋白减少、白细胞减少,其次为恶心、呕吐和腹泻,所有患者未出现３～４级不良反应。结论　洛铂联合５-ＦＵ／ＣＦ毒性反应较轻,患者耐受性较好。推荐使用洛铂４５ｍｇ／ｍ^２联合５-ＦＵ４００ｍｇ／ｍ^２和ＣＦ２００ｍｇ／ｍ^２用于进一步临床研究。     

奥沙利铂累积剂量与蓄积性神经毒性的相关分析

目的　观察奥沙利铂联合氟尿嘧啶和亚叶酸钙（ＦＯＬＦＯＸ４）方案治疗胃肠道恶性肿瘤的不良反应,探讨奥沙利铂神经毒性反应的发生与累积剂量的关系。方法　１１４例胃肠道恶性肿瘤患者应用ＦＯＬＦＯＸ４方案治疗,具体为：奥沙利铂８５ｍｇ／ｍ^２,静滴２ｈ,ｄ_１;亚叶酸钙２００ｍｇ／ｍ^２,静滴２ｈ,注射后立即静脉推注氟尿嘧啶４００ｍｇ／ｍ^２,后予氟尿嘧啶６００ｍｇ／ｍ^２,持续静滴２２ｈ,ｄ_１、ｄ_２,２周为１周期。挽救化疗患者每２个周期评价疗效,至疾病进展。辅助化疗持续６个月,观察不良反应。结果　１１４例患者的神经毒性反应、恶心呕吐及白细胞减少发生率较高,但均较轻微,３～４级不良反应较为少见,其中恶心呕吐发生率为７.９％,白细胞减少１４.０％,血小板减少３.５％以及腹泻３.５％。奥沙利铂累积剂量在１５０～４２０ｍｇ／ｍ^２、４５０～８００ｍｇ／ｍ^２和８２０～９９６ｍｇ／ｍ^２时,神经毒性反应的发生率分别为４３.８％、８９.７％和１００.０％,５例累积剂量≥１００８ｍｇ／ｍ^２患者中有３例出现３级神经毒性反应。结论　ＦＯＬＦＯＸ４方案化疗的不良反应较轻,其中奥沙利铂神经毒性的发生率及严重程度与其累积剂量呈正相关。     

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。     

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。     

同期放化疗治疗局部晚期不可手术的直肠癌近期疗效观察

目的：观察同期放化疗治疗局部晚期不可手术的直肠癌患者的近期疗效及耐受性。方法：３８例经病理证实的局部晚期或局部 区域复发的直肠癌患者接受全盆腔三维适形放疗ＤＴ４６～５０Ｇｙ／２３～２５ｆ,后缩野至肿瘤区继续推量至ＤＴ６４～６６Ｇｙ／３２～３３ｆ,同期接受奥沙利铂１３０ｍｇ／ｍ^２ｄ_１,氟尿嘧啶３５０ｍｇ／ｍ^２ｄ_１～ｄ_５,甲酰四氢叶酸２００ｍｇ／ｍ^２ｄ_１～ｄ_５,４周为１周期,共２个周期。结果：获ＣＲ７例（１９.４％）,ＰＲ１６例（４４.４％）,ＳＤ６例（１６.７％）,ＰＤ７例（１９.４％）,总有效率（ＣＲ＋ＰＲ）为６３.９％;疼痛症状缓解率为１００％;全身状况好转率７２.２％;中位生存时间为２２个月,１年和２年总生存率分别为６７.７％和２１.３％。治疗相关的毒副反应以中性粒细胞减少、腹泻、恶心呕吐以及周围神经毒性反应为主,其３级毒副反应的发生率分别为１９.４％、１６.７％、１３.９％和１１.１％,均无３级以上毒副反应发生。结论：以奥沙利铂为基础的化疗同期联合放疗对局部晚期不可手术直肠癌患者具有较好的姑息治疗作用,其治疗依从性高,治疗相关毒性可以接受,值得临床进一步推广。     

新辅助化疗加同步放化疗治疗局部晚期鼻咽癌的Ⅱ期临床研究

目的：比较新辅助化疗加同步放化疗与单纯同步放化疗治疗局部晚期鼻咽癌的近期疗效和毒副作用。方法：２００４年４月～２００６年５月,８３例Ⅲ ～ⅣＡ期鼻咽癌初治患者采用随机数字表法分为试验组４４例,对照组３９例。两组患者均行相同的常规分割根治性二维放疗;试验组在放射治疗前接受２个周期新辅助化疗,采用ＰＦ方案：顺铂（ＤＤＰ）８０ｍｇ／ｍ^２,ｄ_１,氟尿嘧啶（５-ＦＵ）８００ｍｇ／ｍ^２,ｄ_１～ｄ_５,２１天为１周期。新辅助化疗结束后２周,行同步放化疗,对照组仅行同步放化疗。同步化疗方案：ＤＤＰ４０ｍｇ／ｍ^２,１次／周,共６次。结果：中位随访期２６.７个月,平均随访期（２７.６±１０.９）个月,两组患者基本特征具有可比性。试验组的口腔黏膜炎发生率高于对照组（Ｐ＜０.０５）,其余各项急性毒副反应两组差异均无统计学意义（Ｐ＞０.０５）。试验组与对照组２年局部区域复发率分别为１３.２％和１９.４％（Ｐ＝０.９４６）,２年远处转移率分别为１５.８％和２２.２％（Ｐ＝０.０２１）,２年生存率分别为９２.１２％和８９.１６％（Ｐ＝０.２５１）。结论：初步结果表明,国人局部晚期鼻咽癌采用新辅助化疗加同步放化疗急性毒副反应可以耐受,２年远处转移率较单纯同步放化疗降低,２年局部复发率和生存率相似,推荐行大样本的Ⅲ期临床研究以明确新辅助化疗对局部晚期鼻咽癌是否受益。     

洛铂联合伊立替康治疗复治性小细胞肺癌的临床研究

目的　观察洛铂联合伊立替康方案治疗经ＥＰ方案初治后３～６个月内复发的广泛期晚期小细胞肺癌（ＳＣＬＣ）的疗效和安全性。方法　选取２４例ＳＣＬＣ患者予洛铂３５ｍｇ／ｍ^２,ｄ_１;伊立替康２００ｍｇ／ｍ^２,ｄ_１,２１ｄ为１周期。２个周期后评价疗效和毒副反应,并随访总生存时间（ＯＳ）和疾病进展时间（ＴＴＰ）。结果　２４例均可评价疗效,完全缓解２例,部分缓解８例,总有效率为４１.７％;稳定５例,进展９例,中位ＴＴＰ为４.３个月,中位ＯＳ为７.４个月。毒副反应主要为血液学毒性和消化道反应,３、４级白细胞减少、中性粒细胞减少和血小板减少发生率分别为５０.０％（１２／２４）、４１.７％（１０／２４）和２０.８％（５／２４）;腹泻发生率为８７.５％（２１／２４）,其中３、４级腹泻为５８.３％（１４／２４）。全组无毒性相关死亡。结论　洛铂联合伊立替康方案作为中度敏感复发性ＳＣＬＣ的挽救治疗方案有较好的疗效,毒副反应可以耐受。     

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。     

FOLFIRI方案一线治疗进展期胃癌的临床观察

目的探讨伊立替康（开普拓,IRI,CPT-11）联合氟尿嘧啶（5-Fu）、甲酰四氢叶酸（CF）一线治疗进展期胃癌的疗效及毒性作用。方法对2006年6月至2008年12月采用该方案治疗的进展期胃癌36例患者进行回顾性分析,每例患者至少接受6个周期化疗。用法：CPT-11180mg/m^2,静脉滴注30～90min,第1天;CF400mg/m^2,静脉滴注2h,第1天;5-Fu400mg/m^2,继CF后静脉推注,然后2400mg/m^2,持续静脉滴注,46h,第1天,14d为1个周期。每3～4个周期后按照RECIST实体瘤近期客观疗效评定标准进行疗效评价。结果CR2例,占5.6%;PR14例,占38.9%;SD9例,占25.0%;PD11例,占30.6%;客观有效率（CR＋PR）为44.4%;临床获益率（PR＋CR＋SD）为69.4%,中位疾病进展时间（TTP）5.9个月;中位生存期（MST）10.1个月。不良反应主要为骨髓抑制、延迟性腹泻。结论FOLFIRI方案一线治疗进展期胃癌,疗效较好,毒副反应可耐受,值得临床进一步应用与推广。     

“化疗脑”的研究进展

化疗相关认知损害(chemotherapy-induced cognitive impairment,CICI)又称为"化疗脑"。越来越多的医学文献证据支持常规应用化疗会增加患者认知损害的风险。然而,目前尚未明确CICI的发病机制及其临床特征。在多数情况下,CICI尚处于诊断不足的状态,且现阶段还缺乏有效针对化疗脑的治疗和预防措施,因而影响肿瘤患者的生活质量。当前极有必要在多学科干预下,及时地对CICI进行诊断和处理。     

Second-line chemotherapy in recurrent small cell lung cancer. Results from a crossover schedule after primary treatment with cisplatin and etoposide (EP-regimen) or cyclophosphamide, epirubicin, and vincristin (CEV-regimen)

PURPOSE: To evaluate the benefit of crossover chemotherapy with etoposide and cisplatin (EP) versus cyclophosphamide, epirubicin, vincristine (CEV) at relapse after primary treatment with the opposite regimen in patients with small cell lung cancer (SCLC). Further, to compare the crossover group with patients not receiving chemotherapy. PATIENTS AND METHODS: Among 286 patients diagnosed with relapse after first-line chemotherapy, 120 patients received second-line chemotherapy and 166 patients received best supportive care. Fifty-six patients received EP after previous treatment with CEV, 52 received CEV after EP, and 12 patients were re-treated with the same regimen. Possible prognostic factors in the crossover group were identified at time for first-line chemotherapy and at relapse. The EP therapy comprised five courses of etoposide 100 mg/m(2) IV and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on day 2-4. The CEV-regimen was five courses of epirubicin 50 mg/m(2), cyclophosphamide 1000 mg/m(2), and vincristine 2 mg, all IV on day 1. RESULTS: Patients administered second-line chemotherapy lived significantly longer with median survival 5.3 months compared to 2.2 months in patients with best supportive care only (P<0.001). The best supportive care patients had significantly worse PS status and more resistant disease. The crossover treatment group was well balanced regarding possible prognostic factors prior to initial treatment and at recurrence. No difference in survival was found (P=0.71). Univariate analysis revealed PS at recurrence, objective tumour response from initial chemotherapy, disease stage at first-line, LDH-, NSE-, and ALP at first-line to be significant prognostic factors for survival in the second-line setting. In a multivariate analysis, only PS at time of recurrence remained an independent prognostic factor (P<0.0001). CONCLUSION: Patients administered second-line chemotherapy had significantly longer survival than patients administered best supportive care. However, this difference can be explained by more negative prognostic factors in the best supportive care group. No survival difference between EP and CEV crossover chemotherapy was found. Multivariate analysis revealed PS at time of relapse as the only independent predictor of survival in the crossover recurrent SCLC group.     

ＸＥＬＯＸ方案治疗进展期胃癌的临床观察

目的　探讨奥沙利铂联合卡培他滨（ＸＥＬＯＸ）方案一线治疗进展期胃癌的疗效和不良反应。方法　回顾性分析７１例经病理组织学检查证实的胃癌患者,给予ＸＥＬＯＸ方案化疗,具体为：奥沙利铂１３０ｍｇ／ｍ^２静滴,第１天;卡培他滨１０００ｍｇ／ｍ^２口服,２次／日,第１～１４天,２１天为１周期。记录治疗的有效率（ＲＲ）、疾病进展时间（ＴＴＰ）、总生存时间（ＯＳ）和不良反应。结果　７１例患者共完成３２０个周期化疗,ＲＲ为４３７％（９５％ＣＩ：３６.３％ ～６２.９％）,包括ＣＲ５例（７.０％）,ＰＲ２６例（３６.６％）,中位ＴＴＰ为７.５个月（９５％ＣＩ：６.４～８.５个月）,中位ＯＳ为１１个月（９５％ＣＩ：８.２～１３.８个月）。主要不良反应以１～２级为主,３级不良反应包括恶心呕吐４例、腹泻５例、外周感觉神经症状５例、手足综合征７例和中性粒细胞缺乏６例,无化疗相关性死亡。结论　ＸＥＬＯＸ方案一线治疗进展期胃癌疗效较好,毒副反应可以耐受,使用方便,值得临床进一步研究。     

Phase II study of concurrent administration of doxorubicin and docetaxel as first-line chemotherapy for metastatic breast cancer

OBJECTIVE: To evaluate the efficacy and toxicity of concurrent administration of doxorubicin and docetaxel, without prophylactic use of granulocyte colony-stimulating factor, as first-line chemotherapy in patients with metastatic breast cancer (MBC). METHODS: This multi-institutional study enrolled 40 women; 37 were assessable for efficacy and all 40 patients were evaluated for toxicity. Treatment consisted of 50 mg/m(2) doxorubicin and 60 mg/m(2) docetaxel on day 1 every 3-4 weeks. RESULTS: Patients received a total of 251 cycles of chemotherapy (median, 5 cycles; range, 1-13 cycles). Of the 37 patients assessable for efficacy, 2 had a complete response and 24 had partial responses, which accounted for a 70% objective response rate (95% confidence interval, 53-84%). The median time to treatment failure was 30.1 weeks (range, 3.3-80.7 weeks). Grade 4 neutropenia was observed in 88% of patients and was the most frequent haematological toxicity. Febrile neutropenia was seen in 40% of patients, but no severe infections were observed. Non-haematological toxicity was generally tolerable. There were 2 grade 4 adverse events, which included 1 bleeding duodenal ulcer and 1 hypersensitivity reaction, but grade 3 episodes were infrequent. None of the patients developed congestive heart failure or asymptomatic decrease of left ventricular ejection fraction to less than 50%. Fluid retention syndrome 相似文献   

XELOX方案治疗晚期结直肠癌临床观察

目的比较卡培他滨(希罗达)联合奥沙利铂(XELOX)方案与亚叶酸钙、氟尿嘧啶(5-Fu)联合奥沙利铂(FOLFOX4)方案一线治疗晚期转移性结直肠癌的疗效和不良反应。方法将56例晚期结直肠癌患者随机分为两组,XELOX方案组(28例):卡培他滨(capecitabine,Xeloda)1000mg/m2,Bid,口服,d1~14;奥沙利铂(oxaliplatin)130mg/m2,静脉滴注,持续2h,d1;21 d为1周期。FOLFOX4方案组(28例):奥沙利铂85 mg/m2,静脉点滴2 h,d1;醛氢叶酸200 mg/m2,静脉点滴2 h,d1、2;氟尿嘧啶400 mg/m2,莫非氏管静脉推注d1、2;氟尿嘧啶600 mg/m2,静脉持续滴注(化疗泵),持续22 h,d1、2,14 d为1周期。结果 XELOX组总有效率(RR)50.0%,中位肿瘤进展时间(TTP)7.0个月;FOLFOX4组RR为46.4%,TTP为6.8个月;两组比较各项指标差异无显著性(P>0.05)。不良反应中XELOX组手足综合征发生率高于FOLFOX4组,Ⅲ、Ⅳ度中性粒细胞减少发生率低于FOLFOX4组。结论 XELOX方案一线治疗晚期结直肠癌有确切疗效,不良反应可耐受,与FOL-FOX4方案相当,但XELOX方案用药更为方便,安全性更好。     

Pilot study of daily ifosfamide 1 g/m2 until grade III granulocytopenia as second-line chemotherapy for anthracycline-pretreated advanced soft tissue sarcoma

BACKGROUND AND AIMS: Second-line chemotherapy regimens for advanced soft tissue sarcomas after treatment failure or tumor relapse following anthracyclines are still investigational. The aim of the present study was to assess the activity of ifosfamide with a new schedule for patients with advanced soft tissue sarcoma failing to achieve remission or relapsing following anthracycline-containing regimens; it was attempted to individualize dosages and prevent excessive toxicity. STUDY DESIGN: A second-line chemotherapy regimen of ifosfamide 1 g/m2 daily, with drug withdrawal until the next cycle upon appearance of grade III granulocytopenia, was administered to 21 patients with advanced soft tissue sarcoma. All patients failed to achieve remission or relapsed following a first-line high-dose anthracycline regimen (epirubicin 180 mg/m2 or zorubicin 600 mg/m2 per cycle). The cycles were repeated every four weeks. RESULTS: The median number of cycles applied was three (range, 1-15). The ifosfamide dosage reached was 4-13 g/m2 per cycle, median 5 g/m2. A complete response was achieved in 1/21 patient (5%), no partial responses were observed, 4/21 patients (20%) had stable disease, and 16/21 (75%) had progressive disease. No difference in response and stable disease rates was observed between responders and non-responders to first-line chemotherapy. No difference in the ifosfamide dose reached was noted between patients receiving second-line chemotherapy directly following first-line therapy and those with a time interval between first- and second-line chemotherapy. The granulocytopenia grade III nadir lasted for a median of one day (range, 1-3) and other toxicities including hematological toxicity were mild and infrequent. CONCLUSIONS: In view of the swift regeneration from grade III granulocytopenia, continuation of the study with granulocytopenia grade IV as a limiting factor for ifosfamide dose escalation seems feasible, with the prospect of better efficacy without excessive toxicity.     

A phase-ii study testing weekly platinum derivative combination chemotherapy as 2nd-line treatment in patients with advanced small-cell lung-cancer

A phase II trial was conducted to determine the effectiveness of weekly administration of cisplatin (25 mg/m(2) on day 1) and carboplatin (100 mg/m(2) on day 1) as salvage chemotherapy for patients with small cell lung cancer after first-line chemotherapy without platinum derivatives. Of 40 eligible patients, 38 were evaluable for response. Interval between last course of first-line chemotherapy and first course of salvage therapy was less than 3 months in 34 and greater in 4. Five partial responses (13%; confidence interval at 95%:0.01-0.25) were documented (including 4 in patients with a treatment-free interval <3 months) as well as 8 no change, 21 progressions and 4 early deaths due to malignant disease. Toxicity consisted mainly of moderate thrombopenia and leucopenia. Grade I nephrotoxicity was observed in 6 patients. In conclusion, weekly administration of moderate doses of cisplatin and carboplatin as salvage chemotherapy for small cell lung cancer appeared feasible and was associated with a moderate but definitive anticancer activity.     

伊立替康和奥沙利铂联合氟尿嘧啶类药物一线治疗晚期结直肠癌的临床观察

目的 观察伊立替康(IRI)和奥沙利铂(OXA)联合氟尿嘧啶类药物(5-FU/替吉奥胶囊/卡培他滨)一线治疗晚期结直肠癌的疗效和不良反应.方法 选取有可测量指标的晚期结直肠癌患者35例,第1天应用IRI 130~l60 mg/m2静脉滴注,同时予亚叶酸钙(CF)200 mg/m2静脉滴注后5-FU 400 mg/m2静脉推注,之后5-FU 2400 mg/m2持续泵注44 h;或替吉奥胶囊每次40~60 mg(根据体表面积确定),卡培他滨每次1000 mg/m2,早晚饭后各1次,连续服用10 d,停药4 d;第2天奥沙利铂85~100 mg/m2静脉滴注;14 d为1个周期.每3个周期评价疗效及相关毒性反应.结果 全组35例可评价疗效,中位化疗为4个周期(3~11).客观有效率(ORR)为54.3%(19/35),其中完全缓解(CR)1例,部分缓解(PR)18例.化疗后接受手术的25例患者中,20例患者达到R0切除(57.1%),其中18例患者系初始局部晚期,2例患者初始伴肝转移.所有35例患者在治疗期间,未出现治疗相关性死亡,3级不良反应发生率为54.3%(19/35),其中粒细胞下降发生率为20.0%(7/35),恶心发生率为17.1%(6/35),呕吐发生率为14.3%(5/35),腹泻发生率40.0%(14/35).4级不良反应主要为粒细胞下降发生率,发生率为17.1%(6/35).结论 三药联合方案一线治疗晚期结直肠癌近期疗效高,毒性反应可以耐受.     

卡培他滨单药或联合方案治疗晚期胃癌的临床研究

目的 探讨卡培他滨单药或联合方案治疗晚期胃癌的疗效及安全性.方法 104例晚期胃癌患者接受如下方案治疗:(1)卡培他滨单药组:卡培他滨1000 mg/m2,口服,2次/d,第1～14天,21 d为1个周期.(2)卡培他滨+紫杉类组:卡培他滨1000 ms/m2,口服,2次/d,第1～14天;紫杉醇175 ms/m2,静脉滴注,第1天(或80～90 ms/m2,静脉滴注,第1、8天);或多西紫杉醇65～75mg/m2,静脉滴注,第1天;21 d为1个周期;(3)卡培他滨+铂类组:卡培他滨1000 ms/m2,口服,2 次/d,第1～14天;顺铂15～20 ms/m2,避光静脉滴注2 h,第1～5天;或奥沙利铂130 mg/m2,静脉滴注2 h,第1天;21 d为1个周期.中位治疗3个周期.结果 104例患者的总客观有效率为20.6%,中位生存时间为8.5个月,中位疾病进展时间为5.2个月.在可评价疗效的患者中,一线治疗的客观有效率为40.0%,疾病控制率为76.7%.卡培他滨+紫杉类化疗组的总中位生存期为10.9个月,一线治疗的中位生存期为12.8个月.卡培他滨单药组的不良反应发生率最低.结论 以卡培他滨为基础的治疗方案疗效尚可,患者耐受性好,单药治疗适用于KPS评分<80分的患者,联合紫杉类化疗组的患者生存时间略长,但尚需进一步验证.