恩度联合化疗药物治疗恶性胸腹腔积液的临床观察

目的 观察胸膜腔及腹腔内注入重组人血管内皮抑素(恩度)联合化疗药物治疗癌性胸腹水的疗效及安全性.方法 46例晚期癌性胸、腹水患者,其中实验组23例分别在胸膜腔或腹腔内注入恩度30mg-60mg和化疗药物(胸水者予以DDP 60mg+IL-2 200万U或BLM 60mg+IL-2 200万U;腹水者予以DDP 60mg+5-FU 1.0+ IL-2 200万U)治疗,对照组23例仅在胸膜腔或腹腔内注入化疗药物(胸水者予以DDP 60mg+IL-2 200万U或BLM 60mg+IL-2 200万U;腹水者予以DDP 60mg+5-FU 1.0+ IL-2 200万U)治疗,每7天一次连续给药2-4次,参照RECISE非靶病灶评价方法和WHO毒性反应分级标准,评价客观疗效及不良反应,并由KPS评分变化情况评价患者的生活质量改善.结果 实验组23例患者CR 8 例、PR 9例、NC 6例,有效率73.1%,对照组23例患者CR 6 例、PR 7例、NC 10例,有效率55.6%,两组差异有统计学意义P<0.05;实验组患者QOL改善稳定率为82.6%;对照组患者QOL改善率73.9%;两组差异有统计学意义P<0.05.结论 胸膜腔、腹腔内注入恩度和化疗药物治疗癌性胸腹水有较高的疗效且不良反应少.     

恩度联合顺铂治疗恶性胸腹腔积液及对血管内皮生长因子的影响

[目的]观察恩度联合顺铂胸、腹腔内化疗治疗恶性胸腹腔积液的临床疗效,并探讨其对血管内皮生长因子(VEGF)的影响.[方法]32例晚期恶性胸腹腔积液患者采用顺铂、恩度胸腹腔局部治疗,治疗前后均排尽胸腹腔积液,顺铂60mg每周1次,连续2周;恩度60mg,每周2次,连续2周.1周为1周期,2周期治疗结束后2周评价临床疗效和不良反应.其中19例患者胸腹腔灌注治疗前及治疗后采用ELISA法测定胸腹腔积液VEGF水平.[结果]治疗后胸腹腔积液VEGF水平显著下降,与治疗前比较差异有统计学意义(P＜0.05).所有患者均完成了1～2周的治疗,近期有效率为64.0％.治疗不良反应轻,患者可耐受.[结论]顺铂、恩度序贯灌注治疗恶性胸腹腔积液近期疗效明显,不良反应轻,并可能通过抑制VEGF的表达来达到抑制肿瘤生长和转移.     

检测腹水中血管内皮生长因子对晚期卵巢癌维持治疗的临床意义

目的 评价检测腹水中血管内生长因子水平、腹腔灌注顺铂联合沙利度胺在晚期卵巢癌维持治疗中的临床意义。方法 回顾性分析不能耐受联合或强烈化疗、腹水检测血管内皮生长因子(VEGF)阳性的晚期卵巢癌患者69例的临床资料。腹腔灌注顺铂(DDP)联合沙利度胺(实验组)患者36例,单纯腹腔灌注顺铂患者(对照组)33例,具体方法如下:腹腔灌注顺铂40~60 mg/m²,1次/周,连续应用两次,4周为一周期,同时口服沙利度胺,治疗2个周期评价临床疗效、免疫功能及不良反应。结果 实验组有效率为72.2%,对照组有效率为46.9%,两组差异具有统计学意义。实验组、对照组治疗前与治疗2个周期后腹水VEGF水平相比,差异均具有统计学意义;实验组VEGF的下降幅度高于对照组VEGF的下降幅度。实验组、对照组治疗前与治疗2个周期后T淋巴细胞亚群百分率相比,差异均无统计学意义。实验组Ⅲ~Ⅳ级恶心呕吐发生率低于对照组,两组差异具有统计学意义;而实验组其它Ⅲ-Ⅳ级不良反应(如中性粒细胞减少、血红蛋白减少、疲倦)发生率与对照组相比,两组差异无统计学意义。结论 检测腹水中VEGF水平可提高恶性腹水的诊断率,腹腔灌注化疗药物联合沙利度胺治疗晚期卵巢癌恶性腹水有效率高,降低腹水中VEGF水平,提高生活质量,减轻不良反应,患者耐受性和依从性好。     

腹腔内应用重组人血管内皮抑制素联合氟尿嘧啶治疗恶性腹水的初步探讨

目的：观察腹腔内注入抗肿瘤新药重组人血管内皮抑制素注射液（恩度）联合氟尿嘧啶（５-ＦＵ）治疗恶性腹水的近期疗效和安全性。方法：经细胞学检查确诊的恶性腹水肿瘤患者３６例（食管癌１例、胃癌１０例、结直肠癌１５例、肝细胞癌和胰腺癌各５例）,接受腹腔内注入恩度联合５-ＦＵ的方案治疗,其中５-ＦＵ１.０ｇ以及恩度６０ｍｇ匀速缓慢腹腔注入,每周重复１次;恩度治疗前和治疗中进行腹水ＶＥＧＦ的测定。按照ＷＨＯ腹水评价标准评价近期疗效,参照Ｋａｒｎｏｆｓｋｙ评分（ＫＰＳ）变化评价生活质量（ＱＯＬ）,按照ＮＣＩＣＴＣ３.０版的药物毒性分级标准评价化疗不良反应。用药１周期即可评价不良反应以及近期疗效。结果：全组３６例患者中,接受恩度的周期数为２～４,中位周期数为３,总共完成的周期数为１０２个。获得ＣＲ４例,ＰＲ１３例,即客观有效率（ＲＲ）４７.２％（１７／３６）;腹水缓解持续时间１０～１０５天,中位缓解时间５１天。而ＱＯＬ改善率为５５.６％（２０／３６）。３２例患者治疗前腹水ＶＥＧＦ水平异常升高,根据其治疗后ＶＥＧＦ水平下降的比例将患者分为ＶＥＧＦ下降≥２５％组和ＶＥＧＦ下降＜２５％组,前者有效率和生活质量改善率明显比后者高（Ｐ值分别为０.００３和０.００２）。３～４级不良反应主要与化疗药物有关,包括白细胞下降５.６％（２／３６）、血小板下降２.８％（１／３６）、恶心呕吐５.６％（２／３６）以及腹泻２.８％（１／３６）。结论：腹腔内恩度联合５-ＦＵ治疗恶性腹水是一种安全、可行的治疗手段,具有较好的近期疗效,并能改善生活质量,其作用机制可能与抑制腹水ＶＥＧＦ的水平有关,值得临床进一步深入观察。     

重组人血管内皮抑素联合顺铂腹腔灌注治疗恶性腹水的临床观察

目的 观察腹腔内注入抗肿瘤新药重组人血管内皮抑制素注射液(恩度)联合顺铂(cisplatin,DDP)治疗恶性腹水的临床疗效和不良反应.方法 于2010年1月至2011年1月收集120例恶性腹水患者按腹水严重程度平均分为4组,治疗组腹部经B超定位后行腹腔穿刺置单腔中心静脉导管引腹水后,治疗组1采用恩度30mg/m2 +生理盐水500ml,腹腔灌注3小时,第三日放腹水后予以顺铂45mg/m2 +生理盐水500ml腹腔灌注,夹管两日后放腹水,7天为一个疗程,连续5个疗程.治疗组2以恩度30mg/m2 +生理盐水500ml,腹腔灌注3小时,夹管两日后放水为一个疗程,每7天一次,连续5个疗程;治疗组3以顺铂45mg/m2 +生理盐水500ml腹腔灌注,夹管两日后放水为一个疗程,每7天一次,连续5个疗程;对照组为临终关怀对症处理组,不进行针对肿瘤及腹水的治疗,5周后评价.结果 治疗组1、2、3和对照组的RR分别为57.5%、30.0%、22.5%和0%(P<0.05),疾病控制率(DCR)分别为75.0%、45.0%、35%和5.0%(P<0.05).毒性反应4组比较(P>0.05).结论 重组人血管内皮抑制素注射液联合顺铂能较好地控制恶性腹水,减轻临床症状;不增加化疗药物的不良反应.     

恩度联合化疗药物治疗恶性胸腹腔积液的临床观察

目的：观察胸膜腔及腹腔内注入重组人血管内皮抑素（恩度）联合化疗药物治疗癌性胸腹水的疗效及安全性。方法：46例晚期癌性胸、腹水患者,其中实验组23例分别在胸膜腔或腹腔内注入恩度30mg-60mg和化疗药物（胸水者予以DDP 60mg＋IL-2 200万U或BLM 60mg＋IL-2 200万U;腹水者予以DDP60mg＋5-FU 1.0＋IL-2 200万U）治疗,对照组23例仅在胸膜腔或腹腔内注入化疗药物（胸水者予以DDP60mg＋IL-2 200万U或BLM 60mg＋IL-2 200万U;腹水者予以DDP 60mg＋5-FU 1.0＋IL-2 200万U）治疗,每7天一次连续给药2-4次,参照RECISE非靶病灶评价方法和WHO毒性反应分级标准,评价客观疗效及不良反应,并由KPS评分变化情况评价患者的生活质量改善。结果：实验组23例患者CR 8例、PR 9例、NC 6例,有效率73.1%,对照组23例患者CR 6例、PR 7例、NC 10例,有效率55.6%,两组差异有统计学意义P〈0.05;实验组患者QOL改善稳定率为82.6%;对照组患者QOL改善率73.9%;两组差异有统计学意义P〈0.05。结论：胸膜腔、腹腔内注入恩度和化疗药物治疗癌性胸腹水有较高的疗效且不良反应少。     

重组人血管内皮抑制素联合放化疗治疗肺癌临床研究

目的:观察重组人血管内皮抑制素(恩度)联合放化疗治疗肺癌的近期疗效及毒副反应。方法:经病理学确诊的肺癌患者16例,平均年龄57.2岁,接受恩度治疗同时联合NP、GP或EC方案的全身化疗及体部伽玛刀治疗,其中恩度治疗2-7个周期,平均3.3个周期,非小细胞癌患者化疗用NP、GP方案,小细胞癌患者用CE方案,每组患者均完成2-6个周期化疗,平均2.8个周期。体部伽玛刀治疗局部病灶3.3Gy-4.3Gy/次,共10-12次,靶区总剂量36Gy-46Gy。按照RECIST标准评价近期疗效,参照Karnofsky评分标准(KPS)评价生活质量(QOL)。结果:全组16例患者近期疗效:CR 3例,PR 9例,SD 3例,PD 1例。临床有效率(CR+PR)75%(12/16)。疾病控制率(DCR)94%(15/16)。生活质量评价6例QOL改善,7例QOL稳定,3例患者出现QOL下降。毒副反应较轻,经对症处理均可缓解。结论:恩度与放化疗联合治疗肺癌疗效较好。具有协同作用,安全性亦较好,毒副作用可以耐受。     

重组人血管内皮抑制素联合顺铂胸腔灌注治疗晚期非小细胞肺癌恶性胸腔积液的临床疗效

目的观察重组人血管内皮抑制素(恩度)联合顺铂治疗晚期非小细胞肺癌(NSCLC)恶性胸腔积液的临床疗效和不良反应。方法 90例晚期NSCLC合并恶性胸腔积液患者随机分为联合组(45例)和顺铂组(45例),联合组胸腔内注入恩度45 mg+顺铂40 mg/m2,2次/周,连续3周;顺铂组单用顺铂40 mg/m2胸腔灌注治疗,2次/周,连续3周。评价近期疗效、生活质量(QOL)和不良反应。结果联合组客观有效率(RR)82.22%;顺铂组为51.11%(P<0.05);联合组QOL改善有36例(80.00%),顺铂组为20例(44.44%)(P<0.05)。2组不良反应比较差异无统计学意义。结论恩度联合顺铂治疗晚期NSCLC胸腔积液疗效显著,可明显改善患者的生活质量,且不良反应小。     

腹腔给药治疗恶性腹水近期疗效观察

为了观察腹腔给药治疗60例恶性腹水的疗效,采用腹腔内注入抗癌药+复方苦参注射液的治疗方法.化疗药分别为5-氟尿嘧啶(5-FU)、顺铂(DDP)、卡铂及丝裂霉素,复方苦参注射液40～80 mL/次.结果卵巢癌并腹水有效率(10/14,71.4%)较高,其次为肝癌并腹水(2/5)及胃癌并腹水(4/20,25.0%),其他胰...     

恩度联合化疗治疗晚期恶性肿瘤近期疗效观察

目的:观察恩度(重组人血管内皮抑素注射液,YH-16)联合化疗治疗多种晚期恶性肿瘤的有效性和安全性.方法:经病理组织学或细胞学检查确诊的Ⅳ期恶性肿瘤患者29例,其中非小细胞肺癌(NSCLC) 10例,其他肿瘤19例(大肠癌6例,头颈部鳞癌5例,食管癌、胰腺癌各3例,小细胞肺癌、肾癌各1例),接受恩度联合化疗的方案治疗.每21天为1个周期.按照RECIST标准评价近期疗效,Karnofsky评分(KPS)变化评价生活质量(QOL),按照NCI CTC 3.0版标准评价毒性反应.用药1周期即可评价毒性,2周期后评价疗效.结果:全组29例患者中,25例可以评价客观疗效,29例均可进行安全性评价.总共完成的周期数为71个周期,平均2.4个周期.25例可评价病例中,CR 0例,PR 4例,SD 13例,PD 8例,客观有效率(RR)为16.0%(4/25),疾病控制率 (DCR)为68.0%(17/25);生活质量改善者10例(40.0%),稳定9例(36.0%), 6例(24.0%)下降.G3/4级毒性主要与化疗药物有关,主要有白细胞减少、恶心、呕吐、乏力等.结论:恩度与化疗药物联合使用可以控制和稳定多种晚期恶性肿瘤的发展,改善患者生活质量,且毒性低,安全性好.     

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.     

Costs associated with complications are lower with capecitabine than with 5‐fluorouracil in patients with colorectal cancer

BACKGROUND:

Capecitabine, an oral alternative to 5‐fluorouracil (5‐FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy‐related complications during treatment with capecitabine‐ and 5‐FU–based regimens.

METHODS:

Patients with CRC who received at least 1 administration of capecitabine or 5‐FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure.

RESULTS:

In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5‐FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5‐FU–based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5‐FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469‐$737). In addition, the mean predicted monthly complication cost for 5‐FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892‐$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5‐FU regimens.

CONCLUSIONS:

Capecitabine compared well with 5‐FU–based therapy in patients with CRC and was associated with lower complication rates and associated costs. Cancer 2009. © 2009 American Cancer Society.     

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.