卡培他滨节拍化疗在晚期结直肠癌维持治疗中的疗效观察

摘 要：［目的］ 探讨卡培他滨节拍化疗维持治疗晚期结直肠癌的疗效及安全性。［方法］ 入组69例复发转移性结直肠癌患者,完成联合化疗后疗效评价无疾病进展,根据治疗方法不同分为节拍化疗组、常规化疗组。节拍化疗组32例给予小剂量卡培他滨节拍化疗500mg,2次/d,持续口服,28d为1个周期;常规化疗组37例每次给予卡培他滨 1250mg/m2,2次/d,连续14d,休7d,21d为1个周期;4个周期后观察毒副反应及近期疗效,Kaplan-Meier法绘制中位无进展生存期（PFS）生存曲线图。［结果］ 节拍化疗组与常规化疗组有效率分别为15.63%和16.22%（χ2=0.004,P=0.947）,疾病控制率分别为71.88%和70.27%（χ2=0.021,P=0.884）,差异均无统计学意义。节拍化疗组中位PFS为8.6个月,常规化疗组为7.9个月,差异无统计学意义(χ2=0.367,P=0.554)。节拍化疗组不良反应发生率均低于常规化疗组,且骨髓抑制及手足综合征发生率两组比较差异有统计学意义(P<0.05)。［结论］卡培他滨节拍化疗较常规化疗在结直肠癌晚期维持治疗中显示出等效低毒的特点,值得临床进一步推广。     

卡培他滨节拍化疗在转移性结直肠癌维持治疗中的探索性Ⅱ期研究

背景与目的：转移性结直肠癌患者一线诱导化疗后的维持治疗方案如何选择，尚存在争议。本研究将卡培他滨节拍化疗应用于转移性结直肠癌维持治疗，评估其疗效与安全性。方法：本研究是单臂、单中心探索性研究。接受一线诱导化疗（XELOX、mFOLFOX6、FOLFIRI）18~24周的转移性结直肠癌患者，评估为临床获益后接受卡培他滨500 mg，每天2次口服维持治疗，直至疾病进展。研究首要终点是无进展生存期（progression-free survival，PFS），包括卡培他滨维持治疗的PFS和诱导化疗续贯维持治疗的PFS。次要终点为总生存期（overall survival，OS）和不良反应。结果：2014年10月16日—2017年12月31日于上海交通大学医学院附属瑞金医院接受治疗的转移性结直肠癌患者37例接受节拍化疗维持治疗。中位随访时间15.0个月（4.0~41.4个月）。节拍化疗维持治疗的中位PFS为5.6个月（1.7~38.5个月），诱导化疗续贯维持治疗的中位PFS为11.4个月（6.8~44.3个月）。主要的不良反应为白细胞减少（8/37，21.6%）、恶心呕吐（5/37，13.5%）和手足综合征（3/37，8.1%）。没有1例患者出现3~4级严重不良反应。结论：卡培他滨节拍化疗应用于转移性结直肠癌诱导化疗后维持治疗安全、有效。     

卡培他滨联合沙利度胺治疗晚期结直肠癌39例

[目的]观察卡培他滨(希罗达)联合沙利度胺对晚期结直肠癌的作用.[方法]对我院39例晚期结直肠癌采用希罗达联合沙利度胺应用治疗.希罗达1250mg/m2,每天2次,口服1～14天;沙利度胺100mg,口服1～21天.28天为一个化疗周期,4个周期为一个疗程,完成一个疗程后30天评价疗效,按照WHO实体瘤近期客观疗效评定标准进行评价.[结果]39例病例中3例因药物不良反应未服完1个疗程即中断治疗.36例可评价病例中,CR 3例(8.33%),PR 14例(38.88%),NC¨例(30.56%),PD8例(22.22%),总有效率47.22%.毒性反应主要为神经毒性、便秘和手足综合征.[结论]希罗达联合沙利度胺治疗晚期结直肠癌疗效肯定,安全性较好.     

卡培他滨联合沙利度胺化疗对结直肠癌组织胸苷磷酸化酶表达的影响

目的:探讨卡培他滨联合沙利度胺治疗晚期结直肠癌的近期疗效及癌组织胸苷磷酸化酶的表达。方法:比较卡培他滨联合沙利度胺和5-氟尿嘧啶 亚叶酸 奥沙利铂(FOLFOX4)方案治疗晚期结直肠癌的疗效、不良反应,并采用ELISA方法测定两组患者癌组织中TP含量。结果:卡培他滨联合沙利度胺组疗效优于FOLFOX4组,总有效率分别为50.0%和36.3%(P<0.05);卡培他滨联合沙利度胺组TP浓度均数(211.2±30.5μg/L)显著低于FOLFOX4组(323.4±28.3μg/L)(P<0.005)。结论:卡培他滨联合沙利度胺治疗晚期结直肠癌疗效肯定,安全性较好。     

伊立替康联合卡培他滨二线治疗晚期结直肠癌

目的:观察伊立替康(开普拓,CPT-11)联合卡培他滨(希罗达)治疗一线化疗失败的晚期结直肠癌的疗效及安全性。方法:72例晚期结直肠癌患者,均为经氟脲嘧啶(5-FU)、亚叶酸钙(LV)以及奥沙利铂等药物一线化疗失败者,行CPT-11联合卡培他滨方案治疗,CPT-11180mg/m2,静脉滴注90min,第1天;卡培他滨1250mg/m2,2次/天,第1～14天口服,休息7天,21天为1个疗程,每例患者至少接受4个疗程。按照WHO实体瘤近期客观疗效评定标准进行评价。结果:72例均可评价疗效及不良反应。完全缓解(CR)为0,部分缓解(PR)16例,有效率(RR)22.2%(16/72),稳定(SD)44例,进展(PD)12例。中位疾病进展时间7.6个月(6～28个月),中位生存期12.8个月。不良反应主要为恶心、呕吐、厌食、白细胞减少、脱发和延迟性腹泻,多为Ⅰ～Ⅱ度。结论:伊立替康联合卡培他滨二线治疗晚期结直肠癌,用药方便、疗效肯定,不良反应低,可广泛用于临床。     

卡培他滨联合草酸铂治疗晚期结直肠癌36例的临床研究

目的：研究卡培他滨联合草酸铂治疗晚期结直肠癌的近期疗效和毒副反应。方法：希罗达1250mg／m^2，每日2次口服．第1天～14天：草酸铂(奥沙利铂)130mg／m^2溶入5％葡萄糖注射液250mL中静脉滴注2h，第1天，21天为1周期。至少连用2个周期后评价疗效。结果：37例患者CR3例(8．1％)、PR16例(43．2％)、SD13例(35．1％)、PD5例(13．5％)，有效率51．4％。主要毒副反应为恶心、呕吐、腹泻、血白细胞减少、手足综合征、末梢神经异常、口腔黏膜炎。结论：卡培他滨联合草酸铂化疗晚期结直肠癌的疗效确切，并可提高患者的生活质量，毒副反应小，患者可以耐受。     

卡培他滨联合草酸铂化疗结直肠癌的疗效探讨

  目的 探讨卡培他滨（商品名：希罗达）联合草酸铂（L-OHP）化疗结直肠癌的近期疗效及毒副反应。方法 34例晚期结直肠癌患者，给予卡培他滨2000 mg·m-2·d-1，分2次口服，连服14 d。L-OHP 100 mg·m-2·d-1，持续2 ~ 3 h静脉滴注，第1天应用。21 d为1个周期，至少用2个周期评价疗效，每周期观察毒副反应。结果 34例患者中可评价疗效者31例，CR 2例，PR 14例，SD 10例，PD 5例，总有效（CR+PR）率51.6 %，获益率85.2 %。Ⅲ、Ⅳ度毒副反应为：腹泻2例，感觉神经毒性反应2例，手足综合征1例。Ⅰ、Ⅱ度毒副反应为：腹泻11例，感觉神经毒性反应18例，手足综合征8例，皮肤色素沉着10例，骨髓抑制5例。结论 卡培他滨联合L-OHP治疗晚期结直肠癌疗效可靠，毒副反应可以耐受。     

艾联合化疗治疗老年晚期结直肠癌

目的 研究康艾注射液联合5-氟尿嘧啶、奥沙利铂方案化疗在老年晚期结直肠癌综合治疗中的作用.方法 86例晚期结直肠癌患者随机分成康艾注射液加化疗（治疗组,46例）和单纯化疗组（对照组,40例）,治疗4周期后评价疗效.结果 治疗组与对照组近期疗效分别为76.09%和72.50%（P＞0.05）;治疗组血液及非血液毒性多项低于对照组（P＜0.05）;治疗组生活质量明显改善（P＜0.05）.结论 康艾注射液联合化疗治疗晚期结直肠癌,能减轻化疗毒性及改善生活质量.     

沙利度胺联合方案治疗晚期结直肠癌临床观察

目的探讨沙利度胺联合方案治疗晚期结直肠癌的疗效及安全性。方法45例经病理证实的晚期结直肠癌患者随机分为治疗组和对照组。治疗组22例接受沙利度胺联合卡培他滨和奥沙利铂治疗,对照组23例仅接受卡培他滨联合奥沙利铂治疗。3周为1周期,至少2周期化疗,评价疗效。研究无进展生存期(PFS)、客观有效率（ORR）、疾病控制率（DCR）,并观察安全性及不良反应。结果治疗组DCR为68.2%,而对照组为43.5%,差异有统计学意义（P＜0.05）, PFS 、ORR及患者生活质量两组间差异无统计学意义(P＞0.05)。结论沙利度胺联合方案治疗晚期结直肠癌可显著提高疾病控制率且耐受性良好,值得临床进一步研究。     

卡培他滨节拍化疗在晚期三阴性乳腺癌维持治疗中的疗效观察北大核心

目的:探讨卡培他滨节拍化疗在晚期三阴性乳腺癌患者维持治疗中的近远期疗效、生活质量以及不良反应。方法:将经联合化疗有效的58例晚期三阴性乳腺癌患者随机分为卡培他滨节拍化疗组和卡培他滨常规剂量组两组,每组患者各29例。节拍化疗组患者给予卡培他滨节拍化疗,常规剂量组患者给予常规剂量卡培他滨化疗。治疗2个月后评价近期疗效,每个月评价不良反应,并统计两组患者的中位疾病进展时间、中位生存时间、1年生存率、2年生存率和生活质量的变化。结果:58例患者均可评价疗效。节拍化疗组患者中CR 0例,PR 5例,SD 22例,PD 2例,客观缓解率(ORR)和疾病控制率(DCR)分别为17.2%和93.1%;常规剂量组患者中CR 0例,PR 6例,SD 20例,PD 3例,客观缓解率(ORR)和疾病控制率(DCR)分别为20.7%和89.7%。两组患者的ORR和DCR相比差异无统计学意义(P>0.05)。节拍化疗组患者的中位肿瘤无进展生存时间(PFS)为7.1个月,与常规剂量组患者(6.9个月)比较,差异无统计学意义(P>0.05);节拍化疗组患者的1年、2年生存率分别为72.4%、58.6%,与常规剂量组患者(69.0%、55.2%)比较,差异无统计学意义(P>0.05)。生活质量改善方面,节拍化疗组患者显著优于常规剂量组患者(P<0.05);节拍化疗组患者的主要不良反应为骨髓抑制、消化道反应和手足综合征等,均以Ⅰ-Ⅱ度为主,均可耐受,常规剂量组患者的消化道反应、骨髓抑制、手足综合征等不良反应的发生率和严重程度均显著高于节拍化疗组(P<0.05)。结论:卡培他滨节拍化疗作为晚期三阴性乳腺癌患者的维持治疗,其近远期疗效与常规剂量维持化疗相当,同时可提高患者生活质量,不良反应轻且发生率低,值得临床推广应用。     

卡培他滨节拍化疗联合SIB-IMRT治疗高龄食管癌疗效及安全性分析

目的:观察卡培他滨节拍化疗联合同期加量三维调强放射治疗（SIB-IMRT）方案治疗高龄食管癌患者的疗效及安全性。方法:收集52例年龄≥70岁的Ⅰ-Ⅲ期食管癌未手术患者,化疗方案选择低剂量单药卡培他滨节拍化疗,600 mg/m2,bid,28 d为1个周期,共4个周期,放疗方案选择SIB-IMRT,PGTV 60.2 Gy/28 f,PTV 50.4 Gy/28 f。观察并记录疗效及放化疗不良反应,评价该方案的治疗效果与安全性。结果:全组患者中50例完成治疗,2例因心脏疾病加重而终止放化疗。客观缓解率（ORR）为80.77%,疾病控制率（DCR）为86.54%;患者1、2、3年的生存率分别为78.85%、61.54%、40.38%;放化疗前后KPS评分均值分别为69.62分和84.23分(P<0.05);放化疗前后QLQ-OES24评分分别为（63.56±7.21）和（80.16±6.51）(P<0.05)。不良反应,全组患者发生≥Ⅱ级放射性食管炎7例、≥Ⅱ级放射性气管炎6例、≥Ⅱ级胃肠道反应10例、≥Ⅱ级骨髓抑制19例、≥Ⅱ级手足综合征4例、≥Ⅱ级放射性肺炎3例、肝功能损害3例、食管狭窄2例、食管穿孔0例。结论:卡培他滨节拍化疗联合SIB-IMRT治疗高龄食管癌患者的疗效可靠,不良反应可耐受,安全性高,适合于高龄食管癌患者临床应用。     

Health-related quality of life in colorectal cancer patients

Accurate assessment of quality of life in patients with colorectal cancer is essential in order to inform clinical decisions by providing insights into patients’ experiences of the disease and treatment. This review summarizes the clinical evidence of how treatments for colorectal cancer impact on short- and long-term quality of life. Surgery for colorectal cancer has a short-term detrimental impact on most aspects of quality of life. Chemotherapy in palliative settings often preserves quality of life. Some studies do not demonstrate changes in keeping with clinical expectations. This may be due to insensitive quality of life tools, low numbers of patients, insufficient compliance or patients’ adaptation to changes. An international consensus involving clinicians and methodologists is needed to describe robust standards for quality of life measurement in oncology.     

综合营养干预对晚期大肠癌化疗患者营养状况及生存质量的影响

目的:探讨综合营养干预对晚期大肠癌化疗患者营养状况及生存质量的影响。方法:选择晚期大肠癌患者100例,随机分为对照组和观察组各50例,对照组给予常规饮食,观察组在常规饮食基础上给予个体化膳食指导、教育及肠内肠外营养治疗等综合营养干预,对比治疗前后两组患者近期疗效、营养状况、免疫功能、生存质量及治疗依从性等结果变化。结果:经综合营养干预后,两组化疗有效率与毒副反应比较,差异均无统计学意义（P>0.05）;观察组在营养状况、免疫功能、生存质量及治疗依从性等方面优于对照组（P<0.05）,差异有统计学意义。结论:综合营养干预可有效改善晚期大肠癌化疗患者的营养状况、免疫功能、生存质量及治疗依从性,效果明显,值得临床推广应用。     

Health-related quality of life in patients with metastatic colorectal cancer treated with panitumumab in first- or second-line treatment

Background:

Panitumumab in combination with chemotherapy was evaluated in two pivotal clinical trials in first- and second-line treatment of metastatic colorectal cancer (mCRC), respectively. This analysis compared the health-related quality of life (HRQoL) of patients with or without panitumumab in the two trials.

Methods:

Patients with mCRC were randomised to FOLFOX (first-line trial) or FOLFIRI (second-line trial)±panitumumab. The EuroQoL 5-Dimensions Health State Index (EQ-5D HSI) and Visual Analogue Scale (EQ-5D VAS) were assessed at baseline and monthly follow-up until disease progression. Patients with wild-type KRAS mCRC with baseline and post-baseline HRQoL scores were included. Difference in change from baseline between treatment groups was evaluated using linear mixed and pattern-mixture models.

Results:

In the first-line trial, 576 patients with wild-type KRAS mCRC (284 panitumumab+FOLFOX4 and 292 FOLFOX4 alone) were included in the HRQoL analyses. In the second-line trial, 530 patients with wild-type KRAS mCRC were included in these analyses (263 panitumumab+FOLFIRI and 267 FOLFIRI alone). There was no significant difference in the change in EQ-5D HSI and VAS scores between treatment groups in either trial.

Conclusion:

The addition of panitumumab to FOLFOX4 or FOLFIRI in first- or second-line treatment of wild-type KRAS mCRC significantly improved progression-free survival without compromising HRQoL.     

Modifiable and fixed factors predicting quality of life in people with colorectal cancer

Background:

People with colorectal cancer have impaired quality of life (QoL). We investigated what factors were most highly associated with it.

Methods:

Four hundred and ninety-six people with colorectal cancer completed questionnaires about QoL, functioning, symptoms, co-morbidity, cognitions and personal and social factors. Disease, treatment and co-morbidity data were abstracted from case notes. Multiple linear regression identified modifiable and unmodifiable factors independently predictive of global quality of life (EORTC-QLQ-C30).

Results:

Of unmodifiable factors, female sex (P<0.001), more self-reported co-morbidities (P=0.006) and metastases at diagnosis (P=0.036) significantly predicted poorer QoL, but explained little of the variability in the model (R²=0.064). Adding modifiable factors, poorer role (P<0.001) and social functioning (P=0.003), fatigue (P=0.001), dyspnoea (P=0.001), anorexia (P<0.001), depression (P<0.001) and worse perceived consequences (P=0.013) improved the model fit considerably (R²=0.574). Omitting functioning subscales resulted in recent diagnosis (P=0.002), lower perceived personal control (P=0.020) and travel difficulties (P<0.001) becoming significant predictors.

Conclusion:

Most factors affecting QoL are modifiable, especially symptoms (fatigue, anorexia, dyspnoea) and depression. Beliefs about illness are also important. Unmodifiable factors, including metastatic (or unstaged) disease at diagnosis, have less impact. There appears to be potential for interventions to improve QoL in patients with colorectal cancer.     

老年晚期胃癌患者卡培他滨节律化疗的临床疗效

目的:评价以小剂量卡培他滨持续给药的节律化疗方式治疗老年晚期胃癌的临床疗效和不良反应.方法:研究对象为2007年3月-2009年8月28例老年晚期胃癌患者,给予小剂量卡培他滨的持续给药方式(卡培他滨每次口服500 mg,2次/d,连续服用4周,然后休息1周,每5周为1个化疗周期)进行治疗,共完成2～13个化疗周期,中位化疗周期数为4个.对至少接受过2个化疗周期的患者进行疗效评估.结果:28例患者中,无患者获得完全缓解,4例(14.3%)获得部分缓解,7例(25.0%)疾病稳定,疾病控制率为39.3%(11/28).治疗有效患者的中位疾病进展时间为3.1个月,中位总生存时间为7.2个月.主要不良反应为骨髓抑制、消化系统反应和手足综合征,大多为Ⅰ～Ⅱ度.结论:小剂量的持续长疗程卡培他滨治疗老年晚期胃癌可以有效地控制疾病进展,不良反应较轻,值得作进一步的研究.     

含雷替曲塞化疗方案一线治疗晚期结直肠癌疗效与安全性评价

目的 回顾性分析晚期结直肠癌患者一线使用雷替曲塞联合奥沙利铂(TOMOX)/伊立替康(TOMIRI)化疗的疗效及安全性。 方法 收集江苏省肿瘤医院2012年08月至2017年05月109例TOMOX/TOMIRI方案一线治疗晚期结直肠癌患者的临床资料。 结果 TOMIRI方案和TOMOX方案均无完全缓解的病例,客观缓解率ORR分别为42.3%(30/71)vs. 42.1%(16/38),疾病控制率DCR分别为84.5%(60/71)vs. 89.5%(34/38),无统计学差异(P＞0.05)。分层于原发灶位置时,原发于右半结肠、左半结肠、直肠使用TOMIRI方案的客观缓解率ORR分别为31.8%(7/22)、73.3%(11/15)、35.3%(12/34),差异有统计学意义(P＜0.05)。毒副反应方面,TOMIRI的腹泻发生率高于TOMOX,而周围神经毒性发生率则相反,且都有统计学差异(P＜0.05)。两组总中位PFS为8.0(95%CI,7.1～8.9)个月,总中位OS为27.0(95%CI,19.6～34.4)个月,TOMOX/TOMIRI方案中位PFS分别为7.0(95%CI,5.5～8.5)个月vs. 8.0(95%CI,6.6～9.5)个月,中位OS分别为28.0(95%CI,20.5～35.5)个月vs. 26.0(95%CI,16.83～35.17)个月,均无统计学差异(P＞0.05)。 结论 雷替曲塞联合奥沙利铂/伊立替康一线治疗晚期结直肠癌,疗效不劣于以5-FU为基础的联合化疗方案,TOMOX表现出较好的疗效和安全性,TOMIRI治疗左半结肠癌的缓解率高于右半结肠、直肠癌。     

Mitomycin-C and capecitabine as third-line chemotherapy in patients with advanced colorectal cancer: a phase II study

Purpose The aim of this study was to investigate the therapeutic value and safety of third-line treatment with mitomycin-C (MMC) and capecitabine (Xeloda) in patients with advanced colorectal cancer pretreated with combination regimens including 5-fluorouracil (5-FU), folinic acid (FA) and irinotecan (CPT-11) or 5-FU, FA and oxaliplatin (L-OHP).Patients and methods A total of 21 patients (M/F 16/5, median age 60.0 years) with advanced colorectal cancer, all of whom had developed progressive disease while receiving or within 6 months of discontinuing two sequential chemotherapy lines with 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP, were accrued to this study. At the time of their relapse or progression, cytotoxic chemotherapy, consisting of intravenous MMC 7 mg/m² on therapeutic day 1 plus oral capecitabine 1000 mg/m² twice daily on days 1–14, was initiated. After rest for 7 days, capecitabine 1000 mg/m² twice daily was administered on days 22–35 followed by 7 days rest. Treatment courses were repeated every 6 weeks unless there was evidence of progressive disease, unacceptable toxicity or patient refusal of treatment.Results All the patients were assessable for toxicity and 19 for response. The median number cycles of chemotherapy was two (range one to four). Only 1 patient (4.8%) had a partial response, 4 patients (19.0%) had stable disease, and 14 patients (66.7%) progressed. The median follow-up period was 7.3 months and median time to progression was 2.6 months. The median overall survival was 6.8 months. No toxic deaths occurred. Toxicities of third-line treatment were mild and manageable. As NCI/NIH common toxicity criteria, grade 3/4 anemia, neutropenia and thrombocytopenia occurred in two, one and one patients, respectively.Conclusion Our findings suggest that the combination of MMC and capecitabine in patients with advanced colorectal cancer pretreated with combination regimens including 5-FU, FA and CPT-11 or 5-FU, FA and L-OHP is safe. However, this regimen had a poor response rate and no definitive contribution to increasing patients overall survival time. Further evaluation of other salvage regimens seems to be warranted.