Novel cell-free and concentrated ascites reinfusion therapy (KM-CART) for refractory ascites associated with cancerous peritonitis: its effect and future perspectives

Background  

We have actively carried out cell-free and concentrated ascites reinfusion therapy (CART) for refractory ascites. However, with conventional CART, the membrane becomes clogged after processing about 2 L of cancerous ascites fluid due to the fact that it is rich in cellular and mucous components; it is therefore difficult to process the entire volume of collected ascites.     

静脉和腹腔化疗联合热疗治疗晚期胃癌伴腹水的疗效观察

目的观察多西他赛+氟尿嘧啶(5-Fu)静脉滴注全身化疗和腹腔内灌注顺铂局部化疗及热疗治疗晚期胃癌伴腹水的疗效及不良反应。方法 56例晚期胃癌合并癌性腹水患者采用联合静脉滴注多西他赛+持续静脉滴注5-Fu全身化疗和腹腔内灌注顺铂局部化疗并予局部热疗方案治疗;治疗2⁶个周期,每2个周期后评价疗效、临床受益及不良反应。结果 56例均可评价疗效,其中完全缓解(CR)12例(21.4%),部分缓解(PR)23例(41.1%),总有效率(RR)为62.5%,肿瘤进展时间(TTP)为8.7个月,中位生存期(OS)为13.4个月。腹水CR 15例(26.7%),PR 28例(50.0%),RR为76.7%。主要不良反应为骨髓抑制、消化道反应和口腔黏膜炎,其中Ⅲ6个周期,每2个周期后评价疗效、临床受益及不良反应。结果 56例均可评价疗效,其中完全缓解(CR)12例(21.4%),部分缓解(PR)23例(41.1%),总有效率(RR)为62.5%,肿瘤进展时间(TTP)为8.7个月,中位生存期(OS)为13.4个月。腹水CR 15例(26.7%),PR 28例(50.0%),RR为76.7%。主要不良反应为骨髓抑制、消化道反应和口腔黏膜炎,其中Ⅲ^Ⅳ度白细胞及血小板下降率为19.6%,ⅢⅣ度白细胞及血小板下降率为19.6%,Ⅲ^Ⅳ度血小板下降率为7.1%,ⅠⅣ度血小板下降率为7.1%,Ⅰ^Ⅱ度恶心呕吐、腹泻腹痛的发生率为58.9%,ⅢⅡ度恶心呕吐、腹泻腹痛的发生率为58.9%,Ⅲ^Ⅳ度为5.4%。无治疗相关性死亡。结论静脉化疗(多西他赛+5-Fu)和腹腔化疗(顺铂)的改良DCF方案及热疗是治疗晚期胃癌伴腹水的有效手段,不良反应可以耐受,值得临床进一步研究。     

腹腔热灌注化疗对恶性腹水的疗效观察

目的研究腹腔热灌注化疗对恶性腹水的疗效。方法40例患者随机分为治疗组与对照组,治疗组患者21例,接受腹腔热灌注化疗并内生场热疗,对照组患者19例,接受常温的腹腔灌注化疗。结果腹腔热灌注化疗组完全缓解(CR)6例,部分缓解(PR)10例,平均缓解期5个月,常温腹腔灌注化疗组CR 0例,PR 7例,平均缓解期1个月。两组相比差异有显著意义。腹痛发生率热灌注化疗组2例,常温灌注化疗组1例,两组相比差异无显著意义。结论腹腔热灌注化疗可以明显提高恶性腹水患者的治疗疗效,并不增加其副作用。     

腹腔热灌注化疗对恶性腹水的疗效观察

目的研究腹腔热灌注化疗对恶性腹水的疗效。方法40例患者随机分为治疗组与对照组,治疗组患者21例,接受腹腔热灌注化疗并内生场热疗,对照组患者19例,接受常温的腹腔灌注化疗。结果腹腔热灌注化疗组完全缓解（CR）6例,部分缓解（PR）10例,平均缓解期5个月．常温腹腔灌注化疗组CR0例,PR7例,平均缓解期1个月。两组相比差异有显著意义。腹痛发生率热灌注化疗组2例,常温灌注化疗组1例,两组相比差异无显著意义。结论腹腔热灌注化疗可以明显提高恶性腹水患者的治疗疗效,并不增加其副作用。     

Treatment of malignant ascites with a combination of chemotherapy drugs and intraperitoneal perfusion of verapamil

Purpose

This study was designed to evaluate efficacy, toxicity, and adverse effects of combination of chemotherapy drugs and intraperitoneal perfusion of verapamil in the treatment of malignant ascites.

Methods

Seventy-two patients with malignant ascites were divided into two study groups. Patients in control group (31 cases) received conventional chemotherapy, whereas patients in the combined treatment group (41 cases) were given verapamil intraperitoneally in addition to chemotherapy drugs. Thirty days after the treatment, efficacy, toxicity, and adverse effects were assessed in both study groups.

Results

The treatment of control group led to 1 case of complete remission and 2 cases of partial remission, making the rate of efficacy (complete + partial remission) of 9.7 %. The combined treatment group demonstrated 13 cases of complete remission and 22 cases of partial remission. Thus, the rate of efficacy was significantly higher in the combined treatment group (85.36 %; p < 0.05 vs. control group). Using KPS scores, changes in quality of life were compared before and after the treatment. The quality of life improved in control group by 13.7 %, while combined treatment group showed improvement of 83.5 % (p < 0.05 vs. control group). Further, cumulative survival rate was also significantly higher in the combined treatment group. Treatment toxicity and the rate of adverse effects and intestinal adhesion were not significantly different between study groups.

Conclusions

Intraperitoneal perfusion of verapamil enhances the efficacy of chemotherapy drugs, prolongs survival, and improves the quality of life. Intraperitoneal administration limits cardiotoxicity of verapamil.     

New combination chemotherapy for malignant melanoma--PAV(peplomycin, ACNU, VCR) therapy

A combination chemotherapy (PAV) consisting of peplomycin, ACNU and vincristine (VCR) was given to 30 patients with malignant melanoma and its therapeutic evaluation was performed. The objective response rate was 42.9% for the patients with stage IV metastatic lesions; three of 7 patients showed improvement. This regimen was particularly effective for both cutaneous and subcutaneous metastatic lesions. When PAV was applied as an adjuvant therapy to the operable cases with stage Ib and II, a five-year survival rate was 50% and the result was far better than that of operation alone. Our results in PAV regimen almost identical with those of DAV(DTIC, ACNU, and VCR) regimen as an adjuvant therapy. The result indicates that PAV regimen is useful for the treatment of malignant melanoma since toxic reactions were mild. Further studies are necessary to assess the efficacy of PAV regimen.     

腹腔灌注化疗加热疗治疗恶性腹水疗效观察

目的：观察腹腔灌注化疗加局部热疗治疗恶性腹水的疗效.方法：将70例恶性腹腔积液患者随机分为治疗组（35例）和对照组（35例）.腹腔置管引流腹水后,给予顺铂50mg腹腔灌注化疗,治疗组行腹腔灌注化疗后即刻行腹部局部热疗,对照组仅行腹腔灌注化疗,每周1次,4次后评价疗效.结果：治疗组总有效率（CR＋ PR）为77.14％,对照组总有效率（CR＋PR）为45.71％,两组比较差异有统计学意义（P＜0.05）.结论：腹腔灌注化疗加腹部局部热疗治疗恶性腹水较单纯腹腔灌注化疗疗效好,值得临床推广.     

Intraperitoneal (Ip) administration of cisplatin in combination with systemic chemotherapy in patients with malignant ascites of gastrointestinal cancer: clinical evaluation and pharmacokinetics

Ten patients with carcinomatous peritonitis of gastrointestinal cancer have been treated with administrations of CDDP-Ip (50-150 mg/body), in combination with systemic chemotherapy simultaneously combined with sodium thiosulfate (STS) iv in 4 patients. All patients received transfusions of specific hydration. The pharmacokinetics of CDDP was studied in 4 patients, and the following results were obtained. (1) As for its effect on malignant ascites, according to Koyama's and Saito's criteria, 2 patients showed a complete response, 3 showed a partial response, and 5 showed no change. (2) As for its effect on the primary site, only one patient showed a partial response, and the others no change. (2) As to its side effects, 6 patients manifested nausea and vomiting, and only one showed a mild kidney dysfunction, and no myelosuppression. No significant difference in the side effects between the STS-combined group and the non-STS-combined group was found. (3) Serum CDDP levels were reached maximum 1-2 hours after Ip, and gradually decreased during the beta-phase of iv administration. Significant levels of non-protein-bound CDDP were found in the serum within 4 hours after Ip. These results indicate that the CDDP Ip is safe and useful for carcinomatous peritonitis of gastrointestinal cancer, however the combination of STS might weaken the systemic anti-cancer effect of CDDP by neutralizing the non-protein-bound CDDP in the serum.     

低渗热灌注腹腔化疗治疗胃肠肿瘤恶性腹水的临床研究

目的　探讨低渗热灌注腹腔化疗治疗胃肠肿瘤恶性腹水的临床价值。方法　实验组 32例胃肠肿瘤恶性腹水患者应用大量加热的生理盐水灌洗腹腔结合低渗热灌注顺铂腹腔化疗 ,对照组 40例患者接受单纯顺铂腹腔化疗。结果　实验组腹水控制缓解率 ,1年、2年生存率 ,一般状况改善率均有提高 ,与对照组相比均存在显著差异 (P <0 .0 5) ;两组毒副反应无显著性差异。结论　低渗热灌注腹腔化疗治疗胃肠肿瘤恶性腹水是一种高效、安全、简便的新疗法 ,值得进一步研究和临床推广     

贝伐珠单抗单药或与铂类联合腹腔内注射治疗难治性恶性腹水的临床疗效

目的:观察贝伐珠单抗单药或与铂类联合腹腔内注射治疗由盆腹腔恶性肿瘤引起的难治性恶性腹水的临床疗效。方法:选取2016年1月至2017年12月在长海医院中医妇科收治的伴有难治性恶性腹水的患者10例。治疗方法:腹腔内注射贝伐珠单抗（200 mg）+铂类治疗卵巢癌，注射贝伐珠单抗（200 mg）单药治疗其他盆腹腔恶性肿瘤。按照WHO标准。对其临床疗效、不良反应等进行分析。结果:5名患者（卵巢癌）达到完全缓解，3名（转移性腹膜癌及宫颈癌）部分缓解，其余2名（消化道肿瘤）无变化；整体有效率为80％。仅观察到轻度不良反应，包括1级骨髓抑制和1级恶心和呕吐。所有患者对症治疗后均好转。结论:对于晚期盆腹腔恶性肿瘤特别是卵巢癌导致的难治性恶性腹水，使用腹腔内注射贝伐珠单抗联合铂类的治疗方案安全有效，是控制难治性恶性腹水，提高患者生活质量的优选方案。     

贝伐珠单抗联合含氟尿嘧啶类化疗方案治疗晚期转移性结直肠癌的前瞻性、非干预性、全国多中心临床研究（REACT）

背景和目的 在欧美国家,贝伐珠单抗联合化疗业已成为治疗晚期转移性结直肠癌（mCRC）的标准方案。在我国,贝伐珠单抗的注册临床研究亦显示贝伐珠单抗联合化疗可以提高mCRC客观缓解率和显著改善生存预后。但是,缺乏贝伐珠单抗联合化疗治疗国人mCRC的大样本资料,特别是安全性数据。为此,我们开展了上市后临床研究——REACT研究（REal world study of Avastin in ColorecTal cancer;注册号：NCT 01319877）,系统观察和评价真实世界（real world）中贝伐珠单抗联合氟尿嘧啶类药物为基础的化疗方案治疗国人mCRC的安全性和有效性。方法本研究为一项前瞻性、非干预性、全国多中心的上市后临床研究。根据预设的入排标准,纳入mCRC一线或二线治疗患者,采用贝伐珠单抗联合氟尿嘧啶类药物为基础的常规化疗方案进行治疗。主要终点指标是评估治疗的安全性,次要终点指标为评估总体缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）、KRAS突变状态和贝伐珠单抗用药周期（＜8或≥8周期）对疗效以及生活质量（QoL）的影响。分别采用RECIST 1.1版和NCI-CTC AE 4.03版评价客观疗效和不良反应。结果自2011年3月至2013年12月,24家研究中心共纳入606例mCRC,中位年龄56.6岁（22～81岁）,ECOG PS 0～1占76.7％;其中,一线患者453例,二线患者153例。贝伐珠单抗中位用药周期为5.0个（3.0～8.0个）周期。安全性方面：有102例患者（16.8％）发生≥3级不良事件（AE）;66例（10.9％）发生≥3级可能与贝伐珠单抗有关的AE。特别关注的不良事件（AESI）为高血压（1.8％）、蛋白尿（0.8％）、胃肠穿孔（0.5％）、出血（3.3％）、动脉血栓栓塞（0.3％）、静脉血栓栓塞（1.0％）、肠瘘（0.8％）以及伤口愈合并发症（0.2％）。有效性方面：ORR为18.3％（95％CI：15.3％～21.6％）,一线患者和二线患者的ORR分别为21.0％（95％CI：17.3％～25.0％）和10.5％（95％CI：6.1％～16.4％）（P=0.0035）;中位无进展生存期（mPFS）为9.1个月（95％CI：8.1～9.8个月）;中位总生存期（mOS）为21.9个月（95％CI：17.1～25.7个月）。一线患者与二线患者的mPFS和mOS差异均无统计学意义（mPFS：P=0.6530;mOS：P=0.3695）。按治疗周期划分,应用贝伐珠单抗＜8周期患者的mPFS和mOS分别为7.8个月（95％CI：6.2～8.9个月）和17.6个月（95％CI：14.9～24.8个月）;用药≥8周期患者的mPFS和mOS分别为11.6个月（95％CI：10.9～14.4个月）和30.8个月（95％CI：21.3个月～未达）。用药≥8周期患者的生存获益明显优于＜8周期患者（mPFS：P=0.0001;mOS：P=0.001）。按KRAS突变状态划分,KRAS野生型和突变型患者的mPFS分别为9.8个月（95％CI：6.7～12.3个月）和8.6个月（95％CI：6.2～9.9个月）,差异无统计学意义（P=0.2784）。KRAS野生型和突变型患者的mOS分别为25.7个月（95％CI：16.9个月～未达）和14.3个月（95％CI：10.3～21.9个月）,差异无统计学意义（P=0.1015）。结论REACT研究结果表明,贝伐珠单抗联合氟尿嘧啶类药物为基础的化疗,用于一线或二线治疗国人mCRC患者的总体安全性良好,临床获益明显;贝伐珠单抗联合含氟尿嘧啶类药物化疗使用时间长（≥8周期）的患者比使用时间短（＜8周期）的患者,具有更佳生存获益。这与欧美国家和中国注册临床研究的情况类似,值得临床上进一步推广应用。     

奥沙利铂加白介素-2腹腔热化疗联合静脉化疗治疗老年癌性腹腔积液的临床研究

目的研究奥沙利铂(L-OHP)加白介素-2(IL-2)腹腔热化疗联合静脉化疗治疗老年癌性腹腔积液的疗效和不良反应.方法将42例消化系统肿瘤来源的癌性腹腔积液患者引出腹腔积液后,在加热的5%葡萄糖溶液2 000～2 500 mi中加入L-OHP 85 ms/m2及IL-2(2 MU),用NRL-002型内生场肿瘤热疗系统行腹部局部热疗,腹腔内温度保持在41～43℃,持续60～120 min.腹腔热化疗后第2天,给予静脉化疗,予以亚叶酸钙(CF)0.2 s/m2静滴2 h,氟尿嘧啶(5-FU)0.4 s/m2静推,1.6 g/m2持续静脉输注46 h,每2周重复.结果42例患者近期治疗总有效率为66.67%,其中完全缓解(CR)6例,部分缓解(PR)22例,稳定(NC)6例,无效(PD)8例,中位生存时间(MST)为5.6个月,主要毒性表现为急性腹痛、麻痹性肠梗阻.结论L-OHP加IL-2腹腔热化疗联合静脉化疗治疗老年癌性腹腔积液具有一定的疗效,不良反应轻,且能提高患者生存质量,值得进一步研究.     

得力生腹腔内注射治疗恶性腹水疗效观察

目的:观察得力生注射液腹腔内注射治疗恶性腹水的近期疗效及毒副作用。方法:58例确诊的消化道肿瘤并发癌性腹水患者,随机分为二组:治疗组29例,腹腔内注射得力生;对照组29例,腹腔内注射顺铂,观察患者的近期疗效、生活质量及毒副反应。结果:得力生注射液腹腔内注射有效率为37.9%;而对照组腹腔内注射顺铂的有效率为27.6%,二组比较差异无显著性,但治疗组生活质量(KPS评分)改善者明显高于对照组,且毒副反应发生率明显低于对照组。结论:得力生注射液对恶性腹水有明显的治疗效果,并且具有显著提高患者生存质量的作用。     

Clinical study of combination chemotherapy with mitomycin C, vindesine and cisplatin (MVP therapy) in advanced non-small cell lung cancer

Thirty-seven patients with inoperable non-small cell lung cancer were treated with the combination chemotherapy (MVP therapy) with mitomycin C (8 mg/m2), vindesine (3 mg/m2 X 2) and cisplatin (60 mg/m2). The partial responders were 13 cases (35%), and the median survival time was 271 days. In this study the cisplatin dose was less than in any other report of "MVP" therapy. But both the response rate and the median survival time did not differ from those reported elsewhere. The side effects (bone marrow suppression, renal toxicity, etc.) were mild, and did not prevent the continuance of this therapy. Thus, we could repeat more than 6 courses of "MVP" therapy for 8 patients. Nowadays, it is difficult to obtain complete responders with any chemotherapy for inoperable non-small cell lung cancer. To prolong lives of patients and maintain good quality of life, we recommend chemotherapy with low toxicity in often-repeatable courses.     

射频热疗联合腹腔化疗治疗癌性腹腔积液的疗效观察

目的观察射频热疗联合腹腔化疗治疗癌性腹腔积液的疗效、患者生活质量的改善及其副作用。方法确诊为癌性腹腔积液的患者68例,随机分为两组,采用中心静脉导管胸腔闭式引流尽可能排尽腹腔积液后,实验组给予腹腔灌注顺铂化疗,然后进行腹腔射频热疗。对照组仅为腹腔灌注顺铂化疗。结果治疗组与对照组有效率分别为70.59%和47.06%,P<0.05。主要毒副反应发生率两组相仿。结论射频热疗联合腹腔化疗治疗癌性腹腔积液疗效较好,提高生活质量,安全性高。     

尼妥珠单抗联合化疗治疗恶性胶质瘤

目的 评价尼妥珠单抗联合化疗治疗恶性胶质瘤的疗效及不良反应.方法 尼妥珠单抗200 mg/次,每周1次,连续8周后改为每2周1次;根据患者O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)蛋白表达状况和既往化疗效果,采用个体化的化疗方案.结果 14例恶性胶质瘤患者共接受尼妥珠单抗治疗122次,中位治疗7.5次(2～20次).联合的化疗方案中,替莫唑胺21 d方案10例,替莫唑胺5 d力案2例,替尼泊甙联合顺铂方案1例,替尼泊甙联合尼莫司汀方案1例.PR 3例(21.4%),SD 6例(42.9%),客观有效率为21.4%,疾病控制率(PR+SD)为64.3%.中位无进展生存期(PFS)为4个月(95%CI0.7～7.3),6个月的疾病无进展生存率为30.6%.主要的不良反应为Ⅰ～Ⅱ度的中性粒细胞下降(2例)、血小板下降(2例)、淋巴细胞下降(1例)、恶心呕吐(3例)和无症状的转氨,升高(1例).1例替尼泊甙联合顺铂方案化疗的患者发生Ⅳ度中性粒细胞下降和血小板下降.1例患者出现尼妥珠单抗治疗相关痤疮样皮疹.结论 尼妥珠单抗联合化疗治疗恶性胶质瘤有一定疗效,患者耐受性好,值得进一步扩大病例数开展临床研究.

Abstract：

Objective Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas. Methods The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred.Individualized chemotherapy was administered based on O6-methylguanine-DNA methyltransferase (MGMT)expression and previous chemotherapy responses in combined with nimotuzumab. Results Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 ( median 7.5 times ). Combined chemotherapy regimens included:continuous 21-day temozolomide ( 10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin ( 1 case), and teniposide plus nimustine ( 1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively.Disease control rate ( PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI:0.7-7.3) and PFS at 6 months was 30. 6%. The most common toxicities include grade Ⅰ -Ⅱ neutropenia (2 cases), thrombocytopenia ( 2 cases), lymphopenia ( 1 case), nausea and vomitting ( 3case) and asymptomatic transaminase increase ( 1 case). One patient developed grade Ⅳ neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash. Conclusions Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.     

腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的临床观察

目的 观察腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的疗效和安全性,分析腹水内血管内皮生长因子（VEGF）水平对贝伐珠单抗治疗卵巢癌腹腔积液的临床意义。方法 将46例卵巢癌伴腹腔积液患者随机分为治疗组（n=25）和对照组（n=21）,均应用TC方案（紫杉醇135mg／m2静脉注射d1+卡铂 AUC=5 静脉注射d1）全身化疗,3周重复1次;同时腹腔内给予顺铂40mg／m2+43～45℃ 0.9%生理盐水1500～3000ml热灌注化疗,每2周重复1次,连续治疗6周。治疗组在上述治疗基础上每次热灌注化疗后腹腔内注入贝伐珠单抗300mg,治疗6周。评价患者疗效、生活质量改善及不良反应。酶联免疫吸附法（ELISA）检测46例患者治疗前、后腹水中VEGF水平。结果 治疗组治疗后腹水VEGF水平为（468.30±42.80）pg/ml,明显低于治疗前的（2785.89±305.22）pg/ml（P＜0.05）;治疗组治疗后腹水VEGF水平明显低于对照组治疗后的（820.20±61.49）pg/ml（P＜0.05）。治疗组的有效率（RR）为92.0％（23／25）,对照组为61.9％（13／21）,差异有统计学意义（P＜0.05）。治疗组中VEGF阳性者的RR达1000％,VEGF阴性者为50.0％,差异有统计学意义（P＜0.05）。治疗组的生活质量（QOL）改善率为92.0％,对照组为57.1％,差异有统计学意义（P＜0.05）。46例患者对治疗的耐受良好,无严重不良反应。结论 腹腔内贝伐珠单抗联合腹腔热灌注化疗治疗卵巢癌腹腔积液的疗效优于单纯腹腔热灌注化疗,生活质量明显改善,安全性好,尤其对于腹水VEGF阳性卵巢癌患者更加适合。