顺铂联合多西他赛、培美曲塞及吉西他滨治疗晚期肺腺癌的临床效果比较

目的:比较吉西他滨、培美曲塞、多西他赛联合顺铂三种化疗方案治疗晚期肺腺癌患者的近期疗效与安全性。方法:选择2014年7月至2015年8月在本院肿瘤科住院的经病理或细胞学证实为ⅢB~Ⅳ期肺腺癌的患者共140例,随机分为三组,分别采用多西他赛+顺铂(多西他赛组,n=38)、培美曲塞+顺铂(培美曲塞组,n=56)、吉西他滨+顺铂(吉西他滨组,n=46)三种化疗方案。对三组患者的近期疗效和Ⅲ、Ⅳ度毒性反应的发生情况进行比较。结果:吉西他滨组无完全缓解(CR)患者,部分缓解(PR)患者20例,稳定(SD)患者16例,进展(PD)患者10例,总有效率(RR)43.5%,疾病控制率(DCR)为78.3%;多西他赛组无CR患者,PR患者16例,SD患者12例,PD患者10例,RR42.1%,DCR73.7%;培美曲塞组无CR患者,PR患者28例,SD患者20例,PD患者8例,RR50.0%,DCR为85.7%。三组患者RR及DCR相比较差异无统计学意义(P0.05)。三组化疗方案的主要毒副反应为骨髓抑制,无Ⅲ~Ⅳ度皮疹和末梢神经炎等毒性反应发生。其中,培美曲塞组的严重骨髓抑制即Ⅲ度+Ⅳ度白细胞减少、中性粒细胞减少及血小板减少的发生率明显低于吉西他滨组和多西他赛组(P0.05)。三组化疗方案Ⅲ度+Ⅳ度血红蛋白下降、胃肠道反应、脱发、肝肾功能异常等毒性反应的发生率相比较差异均无显著性(P0.05)。结论:培美曲赛、多西他赛、吉西他滨联合顺铂方案治疗晚期肺腺癌的疗效相当,但培美曲塞组安全性更高。     

多西他赛或紫杉醇联合奈达铂在宫颈癌辅助化疗中的疗效及安全性分析

目的:观察和比较多西他赛或紫杉醇联合奈达铂辅助化疗治疗宫颈癌患者的临床疗效及其安全性。方法:选择45例采用多西他赛联合奈达铂化疗的宫颈癌患者为观察组及45例同期采用紫杉醇联合奈达铂化疗的宫颈癌患者作为对照组,两组均行手术治疗,且术前接受辅助化疗。对比两组临床疗效、手术时间和术后病理状况及不良反应的发生情况。结果:化疗后,观察组临床有效率高于对照组(62.22%vs.55.56%),但组间比较差异无统计学意义(P0.05)。化疗期间,观察组恶心、呕吐、腹痛、腹泻、白细胞、中性粒细胞减少、血红蛋白和血小板减少的发生率均低于对照组,但组间比较差异均无统计学意义(P0.05);观察组神经毒性发生率明显低于对照组,组间比较差异有统计学意义(P0.05)。化疗后,行手术治疗,观察组手术时间低于对照组,但组间比较差异无统计学意义(P0.05);手术后,观察组盆腔淋巴结转移率和宫旁浸润率低于对照组,但组间比较差异无统计学意义(P0.05)。结论:多西他赛联合奈达铂辅助化疗宫颈癌的疗效与紫杉醇联合奈达铂相当,且神经毒性、骨髓抑制方面的发生率明显降低,是临床低毒性且有效的宫颈癌术前新辅助化疗方案。     

培美曲塞联合顺铂治疗晚期非小细胞肺癌的临床疗效观察

目的:探讨培美曲塞联合顺铂治疗晚期非小细胞肺癌(NSCLC)的临床疗效。方法:随机选取我院肿瘤科晚期NSCLC患者177例,随机将其分为3组,培美曲塞联合顺铂治疗(PP组)72例,多西他赛联合顺铂治疗(DP组)53例,吉西他滨联合顺铂治疗(GP组)52例,比较三组治疗方法的临床疗效与不良反应之间的差异,根据临床疗效将PP组分为有效组与无效组,分析培美曲塞联合顺铂治疗晚期NSCLC的影响因素。结果:PP组疾病控制率(DCR)与客观有效率(ORR)均显著高于GP组(均P0.05);PP组与DP组近期疗效之间的比较无显著差异(均P0.05)。PP组的药物毒副作用均显著优于DP组与GP组(均P0.05)。PP组的中位生存期显著高于DP组与GP组(均P0.05),在无吸烟、腺癌与IV期晚期NSCLC患者中,培美曲塞联合顺铂治疗有效率更高。结论:培美曲塞治疗晚期NSCLC的疗效佳,与多西他赛相当并显著优于吉西他滨治疗,药物毒副作用小,且受吸烟状况、病理类型与临床分期影响。     

紫杉醇联合卡铂治疗卵巢癌的临床疗效及对患者血清CA125、CA199、CEA水平的影响

目的:分析紫杉醇联合卡铂治疗卵巢癌的临床疗效及对患者血清糖类抗原125(CA125)、糖类抗原199(CA199)、癌胚抗原(CEA)水平的影响。方法:选择我院2014年1月～2016年12月收治的41例卵巢癌患者,按随机数字表法分为对照组(n=20)和研究组(n=21)。对照组给予紫杉醇联合顺铂治疗,研究组给予紫杉醇联合卡铂治疗。比较两组临床疗效,治疗前后血清CA125、CA199、CEA水平、卡氏评分的变化,不良反应的发生情况和生存情况。结果:治疗后,研究组总有效率显著高于对照组(P0.05);两组血清CA125、CA199及CEA水平均较治疗前明显下降,且研究组低于对照组(P0.05);研究组卡氏评分改善率高于对照组(P0.05),胃肠道反应、神经毒性损伤、骨髓抑制及血液系统毒性率反应发生率低于对照组(P0.05);两组1年生存率及中位生存期比较差异无统计学意义(P0.05)。结论:紫杉醇联合卡铂治疗卵巢癌的疗效明显优于紫杉醇联合顺铂治疗,其能够降低患者血清CA125、CA199及CEA水平,改善患者生活质量。     

调强适形放疗联合化疗治疗局部晚期食管癌的疗效观察

目的:观察调强适形放疗(intensity modulated radiation therapy,IMRT)联合多西他赛、奈达铂方案化疗同步治疗局部晚期食管癌的疗效及安全性。方法:选择66例局部晚期食管癌患者为研究对象,将其随机分为2组,其中常规放疗组(A组)共30例,采用常规照射方法,6/8 MV高能X线,2.0 Gy/次,5次/周;40 Gy/20次后再次定位剂量达60~66 Gy,强调放疗组(B组)共36例,采用强调适应性放疗,6/8MV-X射线照射,以95%等剂量线包绕PTV(计划靶区),处方剂量GTV(肿瘤区)66 Gy/30次,CTV(临床靶区)60 Gy/30次,PTV 60 Gy/30次,每天1次,每周5次。强调放疗组同期接受IMRT和多西他赛、柰达伯化疗,21天1个周期,连续2个周期。治疗结束后根据实体瘤疗效评价标准(RECIST)评定临床疗效;参照WHO毒性反应分度标准评价毒副反应。结果:常规放疗组和强调放疗组的总有效率分别为46.66%和91.67%(x2=17.26,P0.05);常规放疗组的毒副反应发生率显著高于强调放疗组,包括骨髓抑制、放射性食管炎和消化道反应的发生率存在显著差异(P0.05)。结论:调强适形放疗联合多西他赛、奈达铂化疗同步治疗局部晚期食管癌疗效较好,毒副反应可耐受,具有潜在的推广应用价值,值得临床进一步研究。     

培美曲塞与吉西他滨联合卡铂治疗初治老年晚期肺腺癌的临床观察

目的:比较培美曲塞与吉西他滨联合卡铂治疗初治老年晚期肺腺癌的疗效和安全性。方法:收集2010年1月-2011年12月我院≥65岁的Ⅲb期和Ⅳ期肺腺患者84例,随机分为培美曲塞联合卡铂(PC)组:培美曲塞500 mg/m2d1,卡铂按曲线下面积(Auc)=5的剂量水平d2;吉西他滨联合卡铂(GC)组:吉西他滨1000 mg/m2d1,8,卡铂按Auc=5的剂量水平d2,两组1个治疗周期均为21 d,每组42例,比较两组患者的有效率,不良反应及1、2年生存率。结果:PC组和GC组总有效率分别为28.6%和19%(P0.05),疾病控制率分别为73.8%和57.1%(P0.05);两组的中位PFS分别为11.8个月和10.2个月(P0.05),1年生存率分别为52.3%和51.2%(P0.05),2年生存率分别为24.1%和22.4%(P0.05);PC组患者白细胞减少、贫血及血小板减少的不良反应发生率均明显低于GC组(P0.05)。结论:培美曲塞联合卡铂与吉西他滨联合卡铂对初治老年晚期肺腺癌的疗效相近,但前者可能更安全;PC方案可作为老年晚期肺腺癌有效的一线化疗方案。     

TP与GP方案治疗晚期非小细胞肺癌的疗效比较

目的:观察多西紫杉醇联合顺铂(TP)与吉西他滨联合顺铂(GP)治疗晚期非小细胞肺癌(NSCLC)的临床疗效和毒副反应。方法:选取晚期NSCLC60例,随机分为TP组和GP组,每组30例,均完成两个周期化疗。结果:TP组治疗有效率(CR PR)为43．3%,GP组为40．0%,两组比较无显著性差异(P＞0．05)。不良反应主要为骨髓抑制和恶心呕吐;TP组主要为白细胞的下降和末梢神经炎,GP组主要表现为血小板的下降。两组病人毒副反应均可耐受。结论:西紫杉醇或吉西他滨联合顺铂治疗晚期NSCLC均有较好的疗效,毒性反应可以耐受,但应注意不良反应的处理。     

多西紫杉醇联合卡铂治疗老年子宫内膜癌的疗效及安全性

目的:探讨多西紫杉醇与卡铂联合化疗在老年子宫内膜癌患者中的疗效及安全性。方法:选择2010年1月至2016年1月我院收治的子宫内膜癌患者78例作为研究对象,其中年龄60岁的患者42例纳入非老年组,年龄≥60岁的患者36例纳入老年组,均给予多西紫杉醇与卡铂联合化疗。对两组患者一般情况、化疗实施情况、临床疗效以及毒副反应进行观察与比较。结果:两组患者组织学分型有明显差异(P0.05),其他一般资料无显著差别(P0.05)。老年组患者采用低剂量完成化疗的比例明显高于非老年组,差异有统计学意义(P0.05),化疗周期及中断率无显著差异(P0.05)。两组患者临床疗效、血液系统毒副反应及消化系统毒副反应发生率均差异不显著(P0.05)。结论:多西紫杉醇与卡铂联合化疗在老年子宫内膜癌患者中治疗效果与非老年患者类似,安全性尚可,值得临床推广应用。     

88例卵巢上皮性癌行ATP-TCA体外药敏试验结果分析

该研究是探讨三磷酸腺苷生物荧光肿瘤抗癌药物药敏性分析实验（ATP-TCA）在卵巢癌患者化疗中的应用。研究选取88例卵巢上皮性癌新鲜组织行ATP-TCA体外药敏试验,分析结果、计算各种化疗药物敏感性,并与48例对照组患者进行临床近期有效率的比较。结果显示,在体外药敏试验敏感性最强的单药为紫杉醇（51.9%）,敏感性强弱依次为：紫杉醇〉卡铂〉顺铂〉吉西他滨〉拓泊替康〉多西他赛〉依托泊苷〉环磷酰胺〉博来霉素,联合用药方案敏感性较单药增加。药敏组患者临床近期有效率（85.23%）高于对照（68.75%）。ATP-TCA是一种有效的抗癌药物敏感性分析实验,可为卵巢癌患者临床化疗提供个体化的指导方案。     

多西他赛单药与培美曲塞联合顺铂二线治疗老年晚期胃癌的疗效及对患者生活质量的影响

目的:探讨多西他赛单药与培美曲塞联合顺铂二线治疗老年晚期胃癌的疗效及对患者生活质量的影响,为临床用药提供参考。方法:选取我院2014年6月-2017年6月期间收治的120例一线化疗失败的老年晚期胃癌患者,按照随机数字表法将患者分为观察组和对照组各60例,观察组使用培美曲塞联合顺铂治疗,对照组单独使用多西他赛治疗,两组均治疗3个疗程。治疗3个疗程后,采用实体肿瘤的疗效评价标准(RECIST)对两组患者的临床疗效进行评价,参照抗癌药物常见毒副反应分级标准统计患者出现的不良反应,采用生活质量量表评价患者的生活质量,并对所有患者进行为期半年的随访,统计两组患者的生存率。结果:观察组有效率(RR)为30.00%,略高于对照组的25.00%,但两组比较差异无统计学意义(P>0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。治疗后,观察组患者日常生活、社会活动、抑郁、焦虑得分均明显高于对照组(P<0.05)。观察组患者半年生存率为71.67%,明显高于对照组的48.33%(P<0.05)。结论:相比于多西他赛单药治疗,培美曲塞联合顺铂二线治疗老年晚期胃癌能够改善患者生活质量,延长其生存期,安全可靠。     

紫杉醇在治疗晚期或复发性宫颈癌中的应用分析

为了探讨紫杉醇在治疗晚期或复发性宫颈癌中的疗效和安全性,为不适合手术或者放射治疗的患者(包括晚期或复发性宫颈癌患者)注射紫杉醇170 mg/m^2、卡铂5 mg·mL^-1·min^-1、贝伐珠单抗12 mg/kg治疗,每20 d一次,并记录期间的不良反应,直至疾病有所缓解或其毒性有所限制。总共有38名患者接受了平均8个治疗周期(范围2~25),中期随访值为18.5个月(范围2~29)。结果显示,19名患者(50.0%)经历完全反应,而15名患者经历(39.4%)部分反应,平均持续时间为6个月。3级和4级血液学毒性表现为中性粒细胞减少症15例(39.4%)、白细胞减少症13例(34.2%)、贫血症13例(34.2%)、血小板减少症11例(28.9%)。1名接受过骨盆照射的患者发生了2级直肠阴道瘘。本研究表明,紫杉醇、卡铂和贝伐单抗的组合对于晚期或复发性宫颈癌患者是有效且安全的。     

The mechanism of cisplatin-resistance in ovarian cancer

Cisplatin and its analogues have been most frequently used for treatment of human cancer including ovarian cancer. Most advanced ovarian cancer which was fatal before introduction of cisplatin have become to be treated for cure by combination chemotherapy containing cisplatin and its analogues. Thus, combination chemotherapy containing cisplatin and carboplatin have become a standard chemotherapy for treatment of ovarian cancer. Initially, platinum-based combination chemotherapy is associated with a 60-70% clinical response rate. However, the overall 5-year survival rate for advanced ovarian cancer patients is still around 20-30%. This low survival rate is due to the fact that some primary tumors and most recurrent tumors develop drug resistance that leads to treatment failure. Thus, overcoming drug resistance is the key to successful treatment of ovarian cancer. The mechanism of cisplatin-resistance in ovarian cancer is multifactorial, and accumulation of multiple genetic changes may lead to the drug-resistant phenotype. In this review, we report several genetic factors conferring cisplatin-resistance which have been elucidated in our laboratory.     

多柔比星脂质体单药和联合洛铂方案治疗复发卵巢癌的临床研究

目的:评价盐酸多柔比星脂质体单药(PLD)与盐酸多柔比星脂质体联合洛铂治疗复发性卵巢癌的安全性和临床疗效。方法:收集2012年4月至2015年10月我科收治的31例复发晚期上皮性卵巢癌患者,根据患者是否存在铂类耐药分为多柔比星组(单药组)15例及多柔比星+洛铂组(对照组)16例。单药组给盐酸多柔比星脂质体50 mg/m~2,静滴;对照组给盐酸多柔比星脂质体20-30 mg/m~2,洛铂30-50 mg/m~2,静脉滴注,两组每21-28天重复一次,观察和比较两组的临床疗效和毒性反应的发生情况。结果:所有患者完成3-8周期,客观有效率(ORR)为38.7%。单药组为33.3%,对照组为占43.8%,两组ORR比较差异无统计学意义(P=0.411)。单药组骨髓抑制的毒副作用较对照组发生率显著升高高(P=0.019),两组其他毒副反应的发生情况比较差异无统计学意义(P0.05)。单药组和对照组中位生存时间(MST)分别为10个月(95%CI:1.242-18.758)、18个月(95%CI:8.261-27.739),中位无进展生存期(PFS)分别为7个月(95%CI:2.210-13.797)、13个月(95%CI:4.368-21.632),两组MST、PFS比较差异均无统计学意义(P0.277)。结论:聚乙二醇脂质体阿霉素单体或聚乙二醇脂质体阿霉素联合洛铂治疗复发性卵巢癌的疗效相当,而聚乙二醇脂质体阿霉素单体的安全性更高。     

Carboplatin with Decitabine Therapy,in Recurrent Platinum Resistant Ovarian Cancer,Alters Circulating miRNAs Concentrations: A Pilot Study

Objective

Plasma miRNAs represent potential minimally invasive biomarkers to monitor and predict outcomes from chemotherapy. The primary goal of the current study—consisting of patients with recurrent, platinum-resistant ovarian cancer—was to identify the changes in circulating miRNA concentrations associated with decitabine followed by carboplatin chemotherapy treatment. A secondary goal was to associate clinical response with changes in circulating miRNA concentration.

Methods

We measured miRNA concentrations in plasma samples from 14 patients with platinum-resistant, recurrent ovarian cancer enrolled in a phase II clinical trial that were treated with a low dose of the hypomethylating agent (HMA) decitabine for 5 days followed by carboplatin on day 8. The primary endpoint was to determine chemotherapy-associated changes in plasma miRNA concentrations. The secondary endpoint was to correlate miRNA changes with clinical response as measured by progression free survival (PFS).

Results

Seventy-eight miRNA plasma concentrations were measured at baseline (before treatment) and at the end of the first cycle of treatment (day 29). Of these, 10 miRNAs (miR-193a-5p, miR-375, miR-339-3p, miR-340-5p, miR-532-3p, miR-133a-3p, miR-25-3p, miR-10a-5p, miR-616-5p, and miR-148b-5p) displayed fold changes in concentration ranging from -2.9 to 4 (p<0.05), in recurrent platinum resistant ovarian cancer patients, that were associated with response to decitabine followed by carboplatin chemotherapy. Furthermore, lower concentrations of miR-148b-5p after this chemotherapy regimen were associated (P<0.05) with the PFS.

Conclusions

This is the first report demonstrating altered circulating miRNA concentrations following a combination platinum plus HMA chemotherapy regiment. In addition, circulating miR-148b-5p concentrations were associated with PFS and may represent a novel biomarker of therapeutic response, with this chemotherapy regimen, in women with recurrent, drug-resistant ovarian cancer.     

MRI与CT检查对卵巢癌病理分期及复发转移的诊断价值对比研究

摘要 目的：对比磁共振成像（MRI）与计算机断层扫描（CT）检查对卵巢癌病理分期及复发转移的诊断价值。方法：纳入2017年1月～2019年1月于我院接受诊治的卵巢癌患者100例进行研究。所有患者术前均进行MRI与CT检查,并以术后病理组织活检结果为金标准,对比MRI与CT诊断卵巢癌与卵巢癌病理分期的准确率。所有患者均于首次检查6个月后进行复诊,对比MRI与CT诊断卵巢癌复发转移的准确率。结果：MRI诊断卵巢癌的确诊率为94.00%（94/100）,高于CT诊断的81.00%（81/100）;漏诊率为2.00%（2/100）,低于CT诊断的10.00%（10/100）（均P＜0.05）。MRI诊断卵巢癌Ⅰ期、Ⅱ期、Ⅲ期的准确率分别为93.33%（14/15）、95.00%（19/20）、93.33%（28/30）,高于CT诊断的60.00%（9/15）、65.00%（13/20）、73.33%（22/30）（均P＜0.05）。MRI诊断肠管及周围、盆腔淋巴结、腹膜后淋巴结、肝脏等远处侵袭和转移中的准确率分别为100.00%（26/26）、88.89%（24/27）、75.00%（18/24）、95.00%（19/20）,高于CT诊断的76.92%（20/26）、48.15%（13/27）、41.67%（10/24）、45.00%（9/20）（均P＜0.05）。结论：相较于CT检查,MRI检查诊断卵巢癌的准确率更高,漏诊率更低,且在卵巢癌病理分期以及复发转移的诊断准确率更高,具有较好的临床应用价值。     

Conventional Chemotherapy and Oncogenic Pathway Targeting in Ovarian Carcinosarcoma Using a Patient-Derived Tumorgraft

Ovarian carcinosarcoma is a rare subtype of ovarian cancer with poor clinical outcomes. The low incidence of this disease makes accrual to large clinical trials challenging. However, studies have shown that treatment responses in patient-derived xenograft (PDX) models correlate with matched-patient responses in the clinic, supporting their use for preclinical testing of standard and novel therapies. An ovarian carcinosarcoma PDX is presented herein and showed resistance to carboplatin and paclitaxel (similar to the patient) but exhibited significant sensitivity to ifosfamide and paclitaxel. The PDX demonstrated overexpression of EGFR mRNA and gene amplification by array comparative genomic hybridization (log2 ratio 0.399). EGFR phosphorylation was also detected. Angiogensis and insulin-like growth factor pathways were also implicated by overexpression of VEGFC and IRS1. In order to improve response to chemotherapy, the PDX was treated with carboplatin/paclitaxel with or without a pan-HER and VEGF inhibitor (BMS-690514) but there was no tumor growth inhibition or improved animal survival, which may be explained by a KRAS mutation. Resistance was also observed when the IGF-1R inhibitor BMS-754807 was combined with carboplatin/paclitaxel. Because poly (ADP-ribose) polymerase inhibitors have activity in ovarian cancer patients, with and without BRCA mutations, ABT-888 was also tested but found to have no activity. Pathogenic mutations were also detected in TP53 and PIK3CA. In conclusion, ifosfamide/paclitaxel was superior to carboplatin/paclitaxel in this ovarian carcinosarcoma PDX and gene overexpression or amplification alone was not sufficient to predict response to targeted therapy. Better predictive markers of response are needed.     

曲妥珠单抗联合多西紫杉醇在HER-2 阳性晚期乳腺癌中的应用

目的:探讨曲妥珠单抗联合多西紫杉醇在HER-2阳性晚期乳腺癌中的应用。方法:收取2010年2月至2016年1月我院收治的82例HER-2阳性晚期乳腺癌患者作为研究对象,根据不同治疗方案分为观察组及对照组。观察组43例患者给予曲妥珠单抗联合多西紫杉醇治疗,多西紫杉醇以3周为1个周期连续用药4个周期,曲妥珠单抗连续使用8周~52周。对照组39例患者只给予曲妥珠单抗单药治疗。对两组患者临床疗效、临床受益反应指数以及不良反应发生情况进行观察与比较。结果:51P1察组总有效率(60.47%)高于对照组(43.59%),但差异无统计学意义(P0.05)。观察组疾病控制率(90.70%)显著高于对照组(71.79%),差异有统计学意义(P0.05)。观察组临床受益反应有效率(76.74%)显著高于对照组(41.03%)差异有统计学意义(P0.05)。两组患者不良反应无显著差异(P0.05)。结论:曲妥珠单抗联合多西紫杉醇对于HER-2阳性晚期乳腺癌有较好的临床疗效及安全性,患者临床受益高。     

Initial experience with single-agent docetaxel as neoadjuvant therapy in men with locally advanced prostate cancer

Patients with locally advanced prostate cancer have worse outcomes after radical prostatectomy (RP) than patients with more favorable parameters. The findings of large, contemporary, RP series have led investigators at a number of centers to evaluate the potential role of neoadjuvant chemotherapy in patients with locally advanced disease. A currently ongoing study of 28 patients explores the antitumor response of a regimen of single-agent, docetaxel, 40 mg/m(2), administered intravenously on a weekly schedule for 6 weeks to patients with locally advanced prostate cancer before RP. Docetaxel has demonstrated significant antitumor activity in patients with advanced, androgen-independent disease. Study results showed that 75% of patients had reductions in prostate-specific antigen (PSA) levels ranging from 9%-79% at the completion of docetaxel therapy. In 25% of the patients, PSA levels increased by 2%-18% from baseline to completion of chemotherapy. In addition, noncastrate levels of testosterone were maintained in all patients. The docetaxel therapy has also been relatively well tolerated. Reporting of the primary endpoint of pathologic response is pending completion of accrual and surgery.