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。     

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。     

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。     

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。     

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。     

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。     

西妥昔单抗联合ＦＯＬＦＩＲＩ方案治疗晚期大肠癌的临床观察

目的：观察和评价西妥昔单抗（爱必妥）联合ＦＯＬＦＩＲＩ方案治疗国人晚期大肠癌患者的疗效及毒副反应。方法：回顾性分析２００６年６月～２００８年１２月我院经病理证实的晚期大肠癌患者４３例,爱必妥４００ｍｇ／ｍ２,第１次;以后２５０ｍｇ／ｍ^２,每周１次,或者５００ｍｇ／ｍ^２,每２周１次;伊立替康（开普拓）１８０ｍｇ／ｍ^２,第１天,静滴３０分钟;亚叶酸钙２００ｍｇ／ｍ^２,第１、２天,静滴２小时;氟尿嘧啶（５－ＦＵ）４００ｍｇ／ｍ^２,静推,第１、２天,５－ＦＵ６００ｍｇ／ｍ^２,持续静滴２２小时,第１、２天,每２周重复。每例至少接受４周期化疗后评价疗效。结果：全组４３例均可评价,有效率（ＣＲ＋ＰＲ）为３４．９％ （１５／４３）,ＳＤ４８．８％ （２１／４３）,ＰＤ１６．３％ （７／４３）。中位疾病进展时间（ＴＴＰ）８．９个月,中位生存期（ＯＳ）１９．３个月。治疗相关毒副反应主要为皮疹、迟发性腹泻及中性粒细胞减少。结论：西妥昔单抗联合ＦＯＬＦＩＲＩ方案治疗国人晚期大肠癌疗效肯定,可使大部分患者临床获益,其毒副反应可以耐受。     

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。     

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。     

改良ＤＣＦ方案治疗２７例晚期胃癌的临床观察

目的　研究改良的多西紫杉醇联合顺铂（ＤＤＰ）加亚叶酸钙（ＣＦ）和氟尿嘧啶（５ ＦＵ）方案（ｍＤＣＦ）治疗术后复发或不能手术的晚期胃癌的疗效及其毒副作用。方法　对入选的２７例晚期胃癌患者给予国产多西紫杉醇（艾素）５０ｍｇ／ｍ^２ｄ１、ＤＤＰ２５ｍｇ／ｍ２ｄ２～ｄ３、ＣＦ０２ｇ／ｍ^２ｄ２～ｄ３、５-ＦＵ２ｇ／ｍ^２持续静滴４６小时（ｄ２～ｄ３）双周方案全身化疗,观察其疗效及毒副作用。结果　２００６年５月至２００７年７月,２７例胃癌患者平均化疗４.５个周期,ＣＲ１例,ＰＲ１２例,总有效率（ＲＲ）为４８.１％（９５％ＣＩ：３２％ ～６４％）,对紫杉醇耐药者仍然３３.３％（２／６）有效,中位肿瘤进展时间（ＴＴＰ）为６.２个月,中位总生存时间（ＯＳ）１１.８个月。毒副反应主要为骨髓抑制,发生率达１００.０％,且４８.９％为３～４级（其中１６.３％为４级）,出现２例（７.４％）因骨髓抑制停止化疗;口腔黏膜炎、恶心呕吐、周围神经毒性、肝功能损害、腹泻、肾功能损害及心脏毒性发生率分别为５９.２％、５１.９％、４８.１％、４４.４％、２５.９％、１８.５％及１１.１％,大部分为１～２级。没有治疗相关死亡。结论　改良的多西紫杉醇联合ＤＤＰ加ＣＦ和５-ＦＵ双周方案（ｍＤＣＦ）治疗晚期胃癌疗效肯定,骨髓抑制等毒副反应仍然偏高,但有一定的治疗优势,与紫杉醇无完全交叉耐药,值得在临床中进一步改良和验证。     

A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma

Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 mumol/L (range, 7 to 14 mumol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternative methods of administration of the two agents.     

CPT-11联合CF/5-FU方案治疗胃肠道癌的Ⅰ期临床研究

目的探索CPT-11(开普拓)联合CF/5-FU治疗胃肠道癌的最大耐受剂量(MTD)和剂量限制性毒性(DLT).方法 CPT-11初始剂量为120mg/m2,然后150mg/m2,180mg/m2和200mg/m2 iv d1,递增剂量直至出现DLT.CF 200mg/m2iv 2h,然后5-FU 400mg/m2快速静滴,接着5-FU 600mg/m2持续静滴22h,第1天、第2天给药,2周重复.结果 20例胃肠道癌患者共完成化疗111周期,中位数6周期.MTD为200mg/m2,DLT为腹泻和WBC减少.结论我们推荐CPT-11180mg/m2联合CF/5-FR每2周重复的方法,作为国内PS为0～1胃肠癌患者的一线二线化疗方案.     

草酸铂治疗晚期胃癌疗效观察

目的 :观察草酸铂 (L OHP)联合5 -氟尿嘧啶 ( 5 FU )和甲酰四氢叶酸钙(CF)在治疗晚期胃癌中的作用。方法 :L OHP 13 0mg/m2 静脉滴入 ,持续 2h ,d1;CF 10 0mg/m2 静脉滴入 ,d1～d5,5 FU 3 75mg/m2 静脉滴入 ,d1～d5。 2 1d重复。结果 :2 2例患者中 ,完全缓解 (CR) 1例 ,部分缓解 (PR) 12例 ,稳定 (NC) 5例 ,进展 (PD)4例 ,有效率 (CR PR) 5 9 0 9%。毒副反应均比较轻 ,毒性特点是外周神经感觉异常 ,症状可逆。结论 :L OHP联合 5 FU(CF)方案应用于治疗晚期胃癌可以获得比较高的疗效 ,显著提高患者生活质量     

A phase I/II study of oral uracil/tegafur (UFT), leucovorin and irinotecan in patients with advanced colorectal cancer.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose (MTD), toxicity profile and response rate of the oral 5-fluorouracil prodrug UFT (tegafur/uracil) and leucovorin (LV) in combination with irinotecan in patients with advanced or metastatic colorectal cancer. PATIENTS AND METHODS: Patients with histologically proven advanced or metastatic colorectal adenocarcinoma received first-line chemotherapy comprising UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1 to 14, with escalating doses of irinotecan (200-300 mg/m(2)) administered intravenously on day 1 of a three-weekly cycle. Eligibility criteria were standard. The MTD was defined as the dose at which >33% of six patients experienced a dose-limiting toxicity (DLT) during cycle 1. RESULTS: A total of 32 patients were studied. Initially, six patients were treated at each of the irinotecan dose levels (200, 250 and 300 mg/m(2)) combined with UFT 250 mg/m(2)/day and LV 90 mg/day. DLTs consisting of grade 3 or 4 diarrhoea and febrile neutropenia were observed in one of 20 patients at 250 mg/m(2) and three of six patients at the 300 mg/m(2) irinotecan dose level. Having defined the MTD, the 250 mg/m(2) dose level was established as the recommended dose (RD) and expanded to 20 patients in whom treatment was generally well tolerated. The overall response rate was 19%, with five patients having a partial response (PR) and 18 stable disease (SD) out of 32 response-evaluable patients. CONCLUSION: UFT and LV can be safely combined with irinotecan. The RDs for future studies are UFT 250 mg/m(2)/day and LV 90 mg/day given on days 1-14, with irinotecan 250 mg/m(2) administered on day 1, every 3 weeks. This combination is well tolerated and active. Further investigation of UFT and LV in combination with irinotecan is warranted in patients with colorectal cancer.     

Imatinib mesylate for targeting the platelet-derived growth factor beta receptor in combination with fluorouracil and leucovorin in patients with refractory pancreatic, bile duct, colorectal, or gastric cancer--a dose-escalation Phase I trial

BACKGROUND: In previous experimental models, because of its ability to inhibit the activity of platelet-derived growth factor beta receptor, imatinib decreased the interstitial fluid pressure and improved the delivery and efficacy of anticancer drugs, including fluorouracil. The objective of this Phase I study was to define the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of imatinib in combination with fluorouracil and leucovorin in patients with chemotherapy-refractory gastrointestinal cancer. METHODS: A 3-patient cohort dose-escalating study design was used. Patients received leucovorin 200 mg/m2 followed by fluorouracil 2000 mg/m2 as a 24-hour infusion on Days 1 and 2 combined with imatinib on Days -4, -3, -2, -1, 1, 2, 3, and 4. Cycles were repeated every 2 weeks, and the imatinib dose was escalated from 300 mg daily to 700 mg daily in 100-mg steps. RESULTS: Thirty patients were enrolled at 5 dose levels. Frequent and dose-dependant National Cancer Institute Common Toxicity Criteria grade 1-4 adverse events with suspected relation to the treatment were anemia (43%), nausea (33%), fluid retention (27%), elevated serum gamma-glutamyl-transpeptidase (20%), and diarrhea. DLTs were severe neutropenia, central fluid retention, and severe nausea observed in 1 patient each, resulting in an MTD for imatinib of 600 mg per day. There were no differences in imatinib pharmacokinetics before or during chemotherapy. A minor response was observed; and signs of clinical activity, including the resolution of ascites and improvement in performance status, were noted in some patients. CONCLUSIONS: The combination of biweekly fluorouracil/leucovorin and imatinib 600 mg daily given in a week-on/week-off schedule was feasible and safe. Nausea and fluid retention represented the DLTs.     

A phase I study of sequential irinotecan and 5-fluorouracil/leucovorin.

BACKGROUND: Irinotecan (CPT-11) and 5-fluorouracil (5-FU)/leucovorin are active agents in colorectal cancer. A sequence-dependent synergism of SN-38 followed by 5-FU/leucovorin in vitro led us to conduct a phase I trial of CPT-11 followed by 5-FU/leucovorin to determine the maximum tolerated dose (MTD) and toxicities of this regimen and to obtain preliminary indications of its activity in patients with advanced solid tumors. PATIENTS AND METHODS: Fifty-six patients were enrolled in sequential cohorts to receive escalating doses of CPT-11 (90 min infusion) on day 1, followed by leucovorin 20 mg/m(2) (intravenous push) and 5-FU (90 min infusion) on days 2-5 of each 21-day cycle. RESULTS: A total of 347 treatment cycles (median 4, range 1-25) were administered. Dose-limiting toxicities were diarrhea, neutropenia and fatigue. Nine patients with colorectal cancer and one with gastric cancer had partial or minor responses. Eight of the 10 had prior chemotherapy. CONCLUSIONS: CPT-11 and 5-FU/leucovorin, as constituents of this novel mechanism-based schedule, have promising activity in patients who have received prior chemotherapy. The recommended phase II/III starting doses are CPT-11 275 mg/m(2) over 90 min on day 1, and 5-FU 400 mg/m(2) plus leucovorin 20 mg/m(2) on days 2-5 every 21 days. This combination can be administered safely to this schedule if there is strict adherence to the 90 min infusion time for both CPT-11 and 5-FU.     

Phase I study of a weekly schedule of irinotecan, high-dose leucovorin, and infusional fluorouracil as first-line chemotherapy in patients with advanced colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of a weekly schedule of irinotecan (CPT-11), leucovorin (LV), and a 24-hour infusion of fluorouracil (5-FU24h) as first-line chemotherapy in advanced colorectal cancer and to assess preliminary data on the antitumor activity. PATIENTS AND METHODS: Twenty-six patients with measurable metastatic colorectal cancer were entered onto this phase I study. In the first six dose levels, fixed doses of CPT-11 (80 mg/m2) and LV (500 mg/m2) in combination with escalated doses of 5-FU24h ranging from 1.8 to 2.6 g/m2 were administered on a weekly-times-four (dose levels 1 to 4) or weekly-times-six (dose levels 5 to 6) schedule. The dose of CPT-11 was then increased to 100 mg/m2 (dose level 7). RESULTS: Seventy-nine cycles of 5-FU24h/LV with CPT-11 were administered in an outpatient setting. No dose-limiting toxicities were observed during the first cycle at dose levels 1 to 6, but diarrhea of grade 4 (National Cancer Institute common toxicity criteria) was observed in three patients after multiple treatment cycles. Other nonhematologic and hematologic side effects, specifically alopecia and neutropenia, did not exceed grade 2. With the escalation of CPT-11 to 100 mg/m2 (dose level 7), diarrhea of grade 3 or higher was observed in four of six patients during the first cycle; thus, the MTD was achieved. Sixteen of 25 response-assessable patients (64%; 95% confidence interval, 45% to 83%) achieved an objective response. CONCLUSION: The recommended doses for further studies are CPT-11 80 mg/m2, LV 500 mg/m2, and 5-FU24h 2.6 g/m2 given on a weekly-times-six schedule followed by a 1-week rest period. The addition of CPT-11 to 5-FU24h/LV seems to improve the therapeutic efficacy in terms of tumor response with manageable toxicity.     

HLF方案治疗晚期胃癌的临床疗效观察

目的观察拓僖(HCPT)、甲酰四氢叶酸钙(LV)和5-Fu联合组成的HLF方案治疗晚期胃癌的近期疗效及毒副作用.方法 36例晚期胃癌患者均接受HLF方案化疗,其中HCPT 10 mg/m2,静滴,d1～3;LV 100 mg,静滴d1～5;5-Fu 500 mg/m2,静滴10 h,d1～5,28 d为一周期,2～3个周期后判定疗效及毒副作用.结果部分缓解(PR)19例,稳定(NC)14例,进展(PD)3例,总有效率为52.8%.主要毒副作用为白细胞减少和口腔、胃肠黏膜炎,无明显肝肾功能损害.结论 HLF方案为治疗晚期胃癌安全、有效的方案.     

Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer.

PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days. RESULTS: The MTD for patients in group A was Oxal 100 mg/m(2), CPT-11 150 mg/m(2), and FUDR 0.12 mg/kg x 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m(2), LV 400 mg/m(2), and FU 1,400 mg/m(2) by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection. CONCLUSION: Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.     

紫杉醇联合氟尿嘧啶治疗青年进展期胃癌疗效观察

目的:观察紫杉醇联合氟尿嘧啶治疗青年进展期胃癌的临床疗效及不良反应。方法:86例经病理学证实青年Ⅲ-Ⅳ期胃癌患者,随机分为2组:紫杉醇组40例予紫杉醇联合亚叶酸钙及氟尿嘧啶,铂类组予奥沙利铂联合亚叶酸钙及氟尿嘧啶方案化疗,均化疗2个周期以上,每个周期28d。结果:紫杉醇组有效率50%,有末梢神经炎、血液学毒性,胃肠道反应率为25%。含奥沙利铂方案的有效率48%,有末梢神经炎、血液学毒性,胃肠道反应率为44%。2组有效率比较无显著性差异(P>0.05),胃肠道反应率比较有显著性差异(P<0.05)。结论:紫杉醇联合亚叶酸钙及氟尿嘧啶治疗青年进展期胃癌不良反应小,尤其是胃肠道不良反应较小,疗效确切,甚至可以代替铂类做为一线方案首选。