以顺铂为基础不同化疗方案同期放化疗治疗局部中晚期子宫颈癌临床研究

目的 探讨单药顺铂与TP(紫杉醇+顺铂)方案同步放化疗治疗中晚期子宫颈癌的临床疗效及不良反应比较.方法 随机入组44例局部中晚期子宫颈癌患者随机给予单药顺铂方案或TP方案化疗,两组同期放疗均采用盆腔外照射+高剂量率腔内后装.结果 所有患者均完成治疗,治疗结束3月评价其有效率,TP组为66.7 ％,顺铂组为55.0％.1年生存率分别为88.3％、70.0％,差异无统计学意义(P值＞0.05).毒副反应主要是粒细胞减少、胃肠道反应.同期放化疗期间TP组、单药顺铂组发生Ⅲ～Ⅳ度粒细胞减少和Ⅲ～Ⅳ度胃肠道反应分别为16.7％vs5.0％(P＞O.05),12.5％ vs 5.0％(P＞0.05).结论 TP方案与单药顺铂同期放化疗治疗局部中晚期子宫颈癌患者的疗效比较,前者的近期疗效及1年生存率均较后者有所提高,差异无统计学意义(P＞0.05),但从百分率来看,TP组在近期疗效及1年生存率方面均有升高的趋势.尽管联合化疗方案中出现Ⅲ、Ⅳ度放化疗反应的病例数较单药组有所增加,但可以耐受,不影响治疗的完成.     

TPF方案诱导化疗联合同期放化疗治疗局部晚期鼻咽癌的临床研究

目的观察TPF方案诱导化疗联合同步放化疗治疗局部晚期鼻咽癌的疗效及不良反应。方法2009年1月至2010年1月,60例局部晚期鼻咽癌随机分为诱导化疗加同步放化疗（试验组,30例）和同步放化疗（对照组,30例）。两组放疗方法相同,均采用调强放射治疗（IMRT）。试验组TPF方案（多西他赛75mg／m^2,dl,顺铂75mg／m^2,dl,氟尿嘧啶500mg／m^2,d1-5q3W×2）诱导化疗＋同期放化疗（顺铂每周40mg／m^2加同步IMRT）。对照组同期放化疗（顺铂每周40mg／m^2加同步IM-RT）。结果试验组和对照组近期疗效比较差异无统计学意义（P〉0．05）。2年局部控制率试验组为96．6％,对照组为86．6％（P〉0．05）。2年无远处转移生存率试验组为93．3％（28／30）,对照组为70．0％（21／30）（P〈0．05）。试验组Ⅲ／Ⅳ级白细胞及血小板下降明显高于对照组（P〈0．05）。结论诱导化疗加同步放化疗治疗局部晚期鼻咽癌疗效较好,且不良反应可耐受。     

不同化疗方案与调强放疗同期治疗局部晚期鼻咽癌的临床研究

目的：观察顺铂与多西紫杉醇每周方案联合调强放疗同期治疗局部晚期鼻咽癌的临床疗效、不良反应。方法：2003年1月至2008年10月初治的局部晚期鼻咽癌患者63例,年龄13—72岁（中位年龄53岁）,男39例,女24例,其中Ⅲ期42例、Ⅳa期21例。随机分为两组,顺铂加调强放疗组（DDP组）32例,多西紫杉醇加调强放疗组（DTX组）31例,DDP组为放疗期间每周用顺铂25mg／m^2;DTX组为每周用多西紫杉醇25mg／m^2。共用5—6次。调强放疗给鼻咽部肿瘤（PGTVnx）70．6—76．6Gy/（31—33）次、颈部肿大淋巴结（PGTVnd）61．6—70．6Gy／（28—33）次。治疗相关不良反应按国际常见不良反应标准第3版（CTCAEV3．0）分级。结果：DDP组中位随访时间46个月,DTX组44个月;DDP组出现Ⅲ级血液不良反应为2例,无Ⅳ级血液毒性,DTX组出现Ⅲ级血液不良反应3例,Ⅳ级1例,两组均未见粒细胞减少引起的发热及败血症,两组比较无显著性差异（P=0．511）。DDP组Ⅲ度急性口腔粘膜反应为18例,无Ⅳ度反应;DTX组Ⅲ度急性口腔粘膜反应为19例,Ⅳ度1例,两组比较无显著性差异（P=0．504）。两组3年的局部区域控制率、无远处转移率和总生存率分别为92．6％、81．3％、90．5％;93．1％、85．3％、91．8％;两组5年的局部区域控制率、无远处转移率和总生存率分别为85．7％、72．6％、86．6％;93．1％、80．7％、91．8％。两组3年、5年总生存率比较无显著性差异（P〉0．05）。结论：顺铂与多西紫杉醇每周方案联合调强放疗同期治疗局部晚期鼻咽癌的临床疗效基本相似,不良反应多西紫杉醇组稍重,但无统计学意义。     

同期减量放化疗与序贯放化疗治疗Ⅲ期非小细胞肺癌的临床试验

目的探讨和比较同期减量放化疗与序贯放化疗治疗不能手术的Ⅲ期NSCLC的毒副反应和近期疗效。方法病理证实为Ⅲa,Ⅲb期（非恶性胸腔积液）不能手术的初治NSCLC患者80例随机分为2组。同期放化疗组（A）：2周期紫杉醇（减半量）＋顺铂（11P）方案化疗,于放疗第一天同期进行。放疗用三维适形放疗,放疗至总量60Gy-70Gy。同期放化疗结束后继续Te（全量）方案巩固化疗3周期。序贯放化疗组（B）：入组后先行放疗,放疗方案同A组,放疗结束后行Te（全量）方案化疗4—5周期。采用WHO近期疗效评价标准和放化疗毒副反应分级标准进行评定。结果A组近期有效率为80．0％,B组为57．5％（x^2=4．71,P〈0．05）,A组Ⅲ,Ⅳ度急性放射性食管炎,白细胞减少,恶心呕吐和皮肤反应发生率分别为47．5％,42．5％,52．5％和57．5％明显高于B组的25．0％,17．5％,30．0％和17．5％（P〈0．05）;A,B组Ⅲ,Ⅳ度急性放射性肺炎,脱发发生率分别为32．5％,7．5％和20．0％,27．5％（P〉0．05）。结论TP方案减量同期放化疗治疗不能手术的Ⅲ期NSCLC,近期疗效较序贯放化疗组高,副反应经积极对症治疗可以耐受。     

紫杉醇联合顺铂、5-氟尿嘧啶（TPF方案）新辅助化疗治疗晚期鼻咽癌的临床分析

目的：评价紫杉醇联合顺铂（DDP）、5-氟尿嘧啶（5-FU）（TPF方案）治疗晚期鼻咽癌的疗效和不良反应。方法：Ⅲ一Ⅳa期鼻咽癌患者98例随机分为紫杉醇＋顺铂＋5-氟尿嘧啶新辅助化疗联合同期放化疗（治疗组）及以5-氟尿嘧啶＋顺铂组成的同期放化疗组（对照组）。新辅助化疗药用量：紫杉醇135mg,／m^2,d1,顺铂20mg／m^2,d1-5,5-氟尿嘧啶750mg／m^2,d1-5,每21天重复,治疗组所有病人均接受两个疗程TPF方案新辅助化疗。第2程新辅助化疗后14天即开始放疗。两组同期放疗相同。放疗采取6MV X线常规照射,鼻咽部总剂量约DT 70Gy／49天,颈部预防剂量约DT 50—55Gy／35—42天,治疗剂量约60-70Gy／42—49天。比较两组疗效及不良反应。结果：治疗组鼻咽及颈部肿瘤消失的平均剂量小于对照组（P〈0．05）;两组肿瘤临床全消率分别为87．8％与77．6％（P〈0．01）。不良反应主要为粒细胞下降、脱发、口腔黏膜反应及胃肠道反应,均能耐受。结论：紫杉醇联合顺铂、5-氟尿嘧啶新辅助化疗治疗晚期鼻咽癌可提高肿瘤消失率,是治疗晚期鼻咽癌有效安全的方案。     

奈达铂同期放化疗治疗中晚期宫颈癌前瞻性临床研究

目的探讨顺铂同期放化疗与奈达铂同期放化疗治疗中晚期宫颈癌的疗效和不良反应。方法180例中晚期宫颈癌患者随机分为奈达铂同期放化疗组（奈达铂组90例）和顺铂同期放化疗组（顺铂组90例）,观察并比较2组的近期疗效及不良反应。结果奈达铂组近期有效率、1年无复发生存率、1年无转移生存率、2年无复发生存率、2年无转移生存率分别为98．85％、89．66、86．21％、85．06％和80．46％,顺铂组近期有效率、1年无复发生存率、1年无转移生存率、2年无复发生存率、2年无转移生存率分别分别为97．60％（χ2=3．07,P〉0．05）、81．93％（χ2=3．07,P〉0．05）、83．13％（χ2=0．31,P〉0．05）、78．31％（χ2=1．30,P〉0．05）和80．72％（χ2=0．00,P〉0．05）,两组间差异无统计学意义。顺铂组恶心呕吐总发生率及Ⅲ-Ⅳ级发生率分别为52．27％、12．50％,明显高于奈达铂组的27．27％、6．82％（χ2=12．18,P=0．01）,而贫血、白细胞减少、血小板减少、腹泻等不良反应两组间无明显差异。结论奈达铂同期放化疗疗效与顺铂同期放化疗相同,不良反应可以耐受。     

Ⅲ期NSCLC化疗加前程累及野后程适形放疗的临床研究

目的：观察前程累及野后程适形放疗联合健择／去甲长春花碱加顺铂（GP／NP）方案化疗治疗Ⅲ期非小细胞肺癌（non-small cell lung cancer，NSCLC）的疗效。方法：64例NSCLC前瞻性随机分成对照组和试验组，各32例，均同时放、化疗。对照组用EP方案化疗（依托泊苷100mg／m^2，d1～d3；顺铂30nag／m^2，d1～d3），21d为1个周期，放疗采用常规外照射，DT 2Gy／次，每周5次，总DT 50～60Gy。试验组用GP／NP方案化疗（健择1000mg／m^2，d1、d8；去甲长春花碱25mg／m^2，d1、d8；顺铂30mg／m^2，d1～d3），2Id为1个周期，放疗采用前程累及野后程适形放疗，DT 1．8～2．0Gy／次，每周5次，总DT 55～64Gy。结果：对照组总有效率56．3％（18／32），试验组总有效率87．5％（28／32），1、2年生存率分别为37．5％（12／32）、21．9％（7／32）和71．9％（23／32）、46．9％（15／32）．差异有统计学意义，X^2=4．62，P=0．030。结论：前程累及野后程适形放疗联合GP／NP方案化疗治疗Ⅲ期NSCLC有较好疗效，其远期疗效须进一步观察。     

顺铂单药方案与PF方案分别联合放疗治疗局部晚期鼻咽癌的临床观察

目的观察顺铂单药方案与顺铂联合氟尿嘧啶（PF）方案分别联合放疗治疗局部晚期鼻咽癌的近期疗效和毒副反应。方法84例确诊为局部晚期的鼻咽癌患者随机分为两组：治疗组42例,用顺铂80mg／m2,静滴,d1-d2;对照组42例,用顺铂20mg/m2和5-氟尿嘧啶500mg／m2,静滴,d1～d5。两组均以3周为1个疗程,可用2-3个疗程。两组均与放疗联合同步应用,放疗方法均相同,鼻咽部剂量为68～74Gy,颈部淋巴结转移剂量为66—70Gy。结果全程放化疗结束时,治疗组和对照组的鼻咽部肿瘤消退率及颈部淋巴结消退率分别为80．9％、83．3％和83．3％、85．7％。3个月后复查显示,治疗组和对照组的鼻咽部肿瘤消退率及颈部淋巴结消退率分别为88．1％、90．5％和88．1％、88．1％。两组鼻咽部肿瘤消退率及颈部淋巴结消退率近似（P〉0．05）。对照组的毒副反应（口腔黏膜反应、白细胞下降）明显高于治疗组,差异有统计学意义（P〈0．05）。结论两种方案同期放化疗治疗局部晚期鼻咽癌的近期疗效近似,但治疗组的毒副反应较轻,值得临床推广应用。     

泰素帝联合顺铂(TP)与顺铂联合5-FU(PF)方案治疗局部晚期鼻咽癌的比较

背景与目的:泰素帝、顺铂是治疗头颈部肿瘤有效的单药,泰素帝 顺铂(TP)方案联合放疗用于头颈部肿瘤的治疗已完成Ⅱ～Ⅲ期临床试验.本研究通过对比顺铂联合氟尿嘧啶(5-FU)(PF)方案与TP方案对鼻咽癌患者的反应率和毒副反应,探讨局部晚期鼻咽癌患者同期化疗新的化疗方案.方法:自2005年10月1日至2006年3月31日中山大学肿瘤防治中心放疗科二区鼻咽癌住院患者符合入组标准的20例进入试验组(TP组).自2004年3月至2005年9月30日期间符合入组条件的PF方案诱导 同期放化疗的45例病例中随机抽取20例作为对照组(PF组).分别比较两组患者诱导化疗与同期放化疗的近期疗效和不良反应.结果:与PF方案相比,TP方案诱导 同期放化疗实施的平均化疗周期数多(3.85 vs.2.75,P=0.000).诱导化疗后,TP组鼻咽病灶部分缓解(partial remission,PR)18例,稳定(stable disease,SD)2例;颈淋巴结完全缓解(complete remission,CR)7例,PR11例,SD 2例.PF组鼻咽病灶PR 17例,SD 3例;颈淋巴结CR 2例,PR 15例,SD 1例.两组对比差异无统计学意义(P＞0.05).同期放化疗结束后评价,试验组鼻咽灶均达CR,对照组18例达CR;颈淋巴结试验组19例CR,对照组15例CR,残留病灶经进一步处理后无增大或复发.试验组和对照组诱导化疗Ⅲ度及Ⅲ度以上中性粒细胞减少的发生率分别为40.5%和0%;同期放化疗Ⅲ度及Ⅲ度以上中性粒细胞减少的发生率分别为40.5%和10.2%,两组比较差异有统计学意义(P＜0.05),但贫血与血小板减少发生率低(P＜0.05).两者在抗生素使用及静脉营养支持上差异皆无统计学意义(P＞0.05).结论:TP方案治疗鼻咽癌的近期疗效与PF方案相似,不良反应可耐受,远期疗效与毒性尚需进一步研究.     

紫杉醇联合顺铂同步放化疗治疗术后食管癌52例

[目的]探讨紫杉醇联合顺铂同步放化疗治疗术后食管癌的临床疗效。[方法]2000年10月～2007年10月．52例根治术后的Ⅱ～Ⅲ期食管癌患者均接受紫杉醇联合顺铂化疗同步放疗．放疗剂量：50Gy／25F,5周。[结果]28例（54％）患者发生了Ⅲ／Ⅳ级放化疗毒副反应,主要为白细胞下降／中性粒细胞减少、血小板减少和放射性食管炎。中位生存时间为37．2个月,1、3年生存率分别为82．19％、47．13％。2年局控率、无远处转移生存率和无进展生存率分别为60．01％、71．38％和42．01％。[结论]同步放化疗治疗Ⅱ～Ⅲ期术后食管癌患者可行,毒副反应可耐受。     

Experience with Impedance Phlebography Compared with Venography

Venography is a particularly reliable method for the diagnosis of deep venous thrombosis but is not suitable as a screening test. Impedance phlebography represents another attempt to discover a simple, non-invasive and reliable method of detecting deep venous thrombosis. It does not, however, meet these criteria.     

Compliance with guidelines and correlation with outcome in patients with advanced germ-cell tumours

PurposeTo evaluate prior compliance with guidelines in patients treated with salvage chemotherapy for advanced germ-cell tumours (GCT).Patients and methodsData concerning the initial management of patients requiring salvage chemotherapy for GCT at Institut Gustave Roussy between 2000 and 2010 were obtained and correlated with recommendations for treatment. Criteria of non-compliance were defined based on guidelines. Compliance with guidelines, predictive factors for non-compliance and the impact on outcome were analysed.ResultsAmong 82 patients treated in the salvage setting, guidelines to initial treatment were followed in only 41 cases (50%). The most common non-compliance criteria were non-adherence to the planned dose (16%), an inappropriate interval between first-line chemotherapy cycles (16%), the lack of post-chemotherapy surgery (16%) and a long interval to post-chemotherapy surgery (48%). Compliance with standard care was better in cancer centres than in other hospitals (private or public) (Odd Ratio (OR): 6.9, P = 0.001). A poor-risk status according to the International Germ Cell Cancer Collaborative Group (IGCCCG) was also predictive of compliance in univariate but not in multivariate analysis. No significant difference in outcome after salvage chemotherapy was observed. Patients relapsing after non-compliant first-line therapy tended to be more easily salvaged, which is consistent with the fact that their initial treatment was inadequate. Some of these relapses were therefore probably not due to true biologically refractory disease.ConclusionGuidelines for first-line treatment are adhered to in only half the patients requiring salvage chemotherapy. As the only predictive factor for non-compliance was the treating centre, centralisation of patients with GCT in well-trained hospitals should be recommended.     

Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer

BackgroundMethylnaltrexone (MNTX), a peripherally acting μ-opioid receptor (MOR) antagonist, is FDA-approved for treatment of opioid-induced constipation (OIC). Preclinical data suggest that MOR activation can play a role in cancer progression and can be a target for anticancer therapy.Patients and methodsPooled data from advanced end-stage cancer patients with OIC, despite laxatives, treated in two randomized (phase III and IV), placebo-controlled trials with MNTX were analyzed for overall survival (OS) in an unplanned post hoc analysis. MNTX or placebo was given subcutaneously during the double-blinded phase, which was followed by the open-label phase, allowing MNTX treatment irrespective of initial randomization.ResultsIn two randomized, controlled trials, 229 cancer patients were randomized to MNTX (117, 51%) or placebo (112, 49%). Distribution of patients' characteristics and major tumor types did not significantly differ between arms. Treatment with MNTX compared with placebo [76 days, 95% confidence interval (CI) 43–109 versus 56 days, 95% CI 43–69; P = 0.033] and response (laxation) to treatment compared with no response (118 days, 95% CI 59–177 versus 55 days, 95% CI 40–70; P < 0.001) had a longer median OS, despite 56 (50%) of 112 patients ultimately crossing over from placebo to MNTX. Multivariable analysis demonstrated that response to therapy [hazard ratio (HR) 0.47, 95% CI 0.29–0.76; P = 0.002) and albumin ≥3.5 (HR 0.46, 95% CI 0.30–0.69; P < 0.001) were independent prognostic factors for increased OS. Of interest, there was no difference in OS between MNTX and placebo in 134 patients with advanced illness other than cancer treated in these randomized studies (P = 0.88).ConclusionThis unplanned post hoc analysis of two randomized trials demonstrates that treatment with MNTX and, even more so, response to MNTX are associated with increased OS, which supports the preclinical hypothesis that MOR can play a role in cancer progression. Targeting MOR with MNTX warrants further investigation in cancer therapy.Clinical trials numberNCT00401362, NCT00672477.     

Living with secondary breast cancer: coping with an uncertain future with unmet needs

JOHNSTON S.R.D. (2010) European Journal of Cancer Care 19 , 561–563 Living with secondary breast cancer: coping with an uncertain future with unmet needs     

奥沙利铂联合羟基喜树碱治疗晚期胃癌临床分析

背景与目的体外及体内的临床研究显示,奥沙利铂(L-OHP)对多种肿瘤有显著抑制作用并与绝大多数抗癌药物具有相加或协同细胞毒作用.本文旨在观察L-OHP联合羟基喜树碱(HCPT)治疗晚期胃癌的近期疗效和患者耐受性,并与传统的化疗方案进行对比.方法采用非随机的分组方法将43例晚期胃癌患者分为L-OHP+HCPT方案组(治疗组)与Vp-16+CF+5-FU(ELF)方案组(对照组),其中男性28例,女性15例,中位年龄59岁,KPS评分≥60,观察两组的近期疗效和患者耐受性.结果治疗组24例有效率58.3%(14/24),对照组19例有效率42.1%(8/19).治疗组有效率高于对照组,两组差异有显著性(P<0.05).两组不良反应主要是骨髓抑制、恶心、呕吐、口腔炎、周围神经炎、静脉炎、脱发等,均在Ⅰ、Ⅱ度范围内.结论L-OHP联合HCPT方案治疗晚期胃癌疗效较好,不良反应可以耐受.     

Varicella-Zoster Virus Prophylaxis with Low-Dose Acyclovir in Patients with Multiple Myeloma Treated with Bortezomib

BackgroundVaricella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population.Patients and MethodsWe studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m² was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently.ResultsA total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment.ConclusionVaricellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.     

Pseudomembranous colitis associated with chemotherapy with 5-fluorouracil

Pseudomembranous colitis is frequently associated with antibiotics and more rarely with chemotherapeutic agents such as 5-fluorouracil. The objective of this study is to show that it is possible to confuse this infection with chemotherapy associated toxicity. We present a 54 year old woman who underwent surgery for colorectal cancer and in the first cycle of chemotherapy with 5-fluorouracil developed pseudomembranous colitis. We detected the toxin B of Clostridium difficile in stools and we began early antibiotic treatment. Thus, in patients with post chemotherapy neutropenia and diarrhoea that develop negatively, we have to rule out this infection.