贝伐单抗联合顺铂腹腔灌注治疗恶性腹水疗效观察

目的探讨贝伐单抗联合顺铂腹腔灌注治疗恶性腹水近期疗效及不良反应。方法将34例恶性腹水患者分成2组,治疗组18例,予贝伐单抗(安维汀)5mg/kg联合顺铂60mg/m2,腹腔灌注,第1天;对照组16例,予顺铂60mg/m2,腹腔灌注,第1天。每4周重复,2～3疗程后评价疗效。结果贝伐单抗联合顺铂治疗组CR7例,PR8例,NC/PD3例,ORR为83.3%;对照组CR2例,PR5例,NC/PD9例,ORR为43.8%。治疗组生活质量改善率为88.9%,对照组为56.3%两组患者不良反应以Ⅰ～Ⅱ度骨髓抑制及胃肠道反应为主。结论与传统顺铂单药相比,贝伐单抗联合顺铂组显著提高恶性腹水患者客观缓解率,生活质量明显改善且安全性好,值得进一步临床验证。     

替吉奥联合顺铂腹腔热灌注化疗治疗胃癌合并腹水17例临床观察

目的观察分析替吉奥联合顺铂腹腔热灌注化疗治疗胃癌合并腹水的临床效果。方法 17例胃癌合并腹水患者,替吉奥连续服用14 d,停药7 d,21 d为1个周期。顺铂40 mg加入0.9%生理盐水1000 m L加热至43℃腹腔内灌注,连用3 d,21 d为1个周期,2个周期后行疗效评价。结果 17例患者都进行疗效及安全性评价,CR 2例,PR 7例,PD+SD 8例,腹水有效率(CR+PR)为52.9%,不良反应主要是胃肠道反应和血液学毒性。胃肠道反应较轻,Ⅲ~Ⅳ的白细胞减少占11.70%(2/17)。结论替吉奥胶囊联合DDP方案治疗胃癌合并腹水对腹水有较高的缓解率,不良反应轻,有临床应用价值。     

大剂量顺铂双途径化疗治疗恶性卵巢生殖细胞肿瘤的临床观察

11例经手术和病理证实为卵巢恶性生殖细胞肿瘤的患者。共接受了66个疗程大剂量顺铂“双途径化疗”。顺铂按90～150mg／m2剂量溶解于生理盐水中注入腹腔，同时静滴硫代硫酸钠缓解其全身毒性。结果即便顺铂剂量达到150mg／m2．也无肾脏毒性和骨髓抑制及局部并发症发生；近期疗效完全有效率为81％。提示大剂量顺铂“双途径化疗”可明显减轻顺铂所致的全身毒性，提高用药剂量和疗效，是安全有效的治疗方法。     

腹腔化疗联合局部热疗治疗消化道肿瘤恶性腹水的临床研究

目的评价腹腔化疗联合局部热疗治疗消化道肿瘤恶性腹水的疗效和毒性反应。方法将31例临床确诊为消化道肿瘤恶性腹水患者应用腹腔灌注化疗药物氟尿嘧啶（5-FU）1.0g,顺铂（DdP）40～60mg,每周1次;且配合局部热疗,每周2次。连续治疗3或4周后观察疗效。结果1症状缓解：腹胀、纳差、腹痛症状平均完全缓解44/50（88%）例,减轻5/50（10%）例,无效2/50（4%）例。2近期疗效：完全缓解（CR）8/31（25.8%）例,部分缓解（PR）11/31（35.5%）例,有效（CR＋PR）19/31（61.3%）例。3毒副反应主要表现为0-I度胃肠道反应及骨髓抑制,部分患者出现腹部隐痛,经对症处理后均好转,不影响治疗。结论腹腔灌注化疗配合局部热疗治疗消化道肿瘤恶性腹水疗效明显,毒副作用较轻,治疗安全,适应临床应用。     

顺铂腹腔热灌注并微波局部热疗对癌性腹水的疗效观察

目的观察顺铂腹腔热灌注联合微波局部热疗治疗癌性腹水的临床疗效及副反应。方法64例癌性腹水病人随机分为两组,治疗组32例采用顺铂腹腔热灌注并微波局部热疗;对照组32例单用顺铂腹腔热灌注治疗。结果治疗组有效率及KPS评分较对照组明显提高,两组比较差异有统计学意义。结论顺铂腹腔热灌注并微波热疗能显著提高癌性腹水的治疗效果,改善病人生存质量,值得临床推广应用。     

腹腔内灌注紫杉醇治疗恶性腹水近期疗效

目的：观察紫杉醇腹腔内灌注对治疗恶性腹水的近期疗效。方法18例恶性腹水患者随机、双盲分为紫杉醇组和顺铂组,采用对照研究,分别于腹腔积液尽量排净后,给予腹腔内灌注紫杉醇或顺铂。每周1次,连续3周。结果紫杉醇组临床总有效率为88.9%,顺铂组临床总有效率为55.6%,两组相比差异具有统计学意义（P〈0.05）。紫杉醇组生活质量改善较顺铂组明显,两组药物不良反应差异无统计学意义（P〉0.05）。结论腹腔内灌注紫杉醇治疗恶性腹水近期疗效较好,操作简单方便、不良反应少,是一种前景较好的治疗方法。     

不同剂量顺铂腹腔灌注联合全身化疗治疗无腹水期卵巢癌的临床观察

目的:观察不同剂量顺铂腹腔灌注联合全身化疗治疗无腹水期卵巢癌的疗效和不良反应。方法:43例无腹水期卵巢癌患者随机分成高剂量组和低剂量组。高剂量组(22例)腹腔灌注顺铂75mg·m-2;低剂量组(21例)腹腔灌注顺铂50mg·m-2。同时配合全身化疗,紫杉醇135mg·m-2,第1天,静脉滴注,每3周重复1次。3周期后评价疗效。结果:高剂量组和低剂量组有效率分别为86.36%和52.38%,2组比较有显著性差异(P<0.05);高剂量组和低剂量组一般状况改善率分别为81.82%和47.62%,2组比较有显著性差异(P<0.05);高剂量组Ⅲ～Ⅳ度恶心、呕吐的发生率达31.82%,高于低剂量组9.52%(P<0.05)。结论:高剂量顺铂腹腔灌注联合全身化疗临床疗效确切,并且可明显改善患者的生存质量,但不良反应发生率较低剂量组高。     

香菇多糖联合顺铂腹腔灌注治疗肿瘤患者腹腔积液的临床疗效

目的探讨分析生物反应调节剂香菇多糖联合顺铂腹腔灌注治疗肿瘤患者腹腔积液的疗效。方法将30例肿瘤合并腹腔积液患者,分别给予顺铂和香菇多糖联合顺铂腹腔灌注治疗,并对比分析治疗效果。结果实验组4例NC,9例PR,2例CR,总有效率为73.33%,对照组5例NC,8例PR,2例CR,总有效率为66.67%。两组患者临床治疗效果对比差异显著(P<0.05),具有统计学意义。结论香菇多糖联合顺铂腹腔灌注治疗肿瘤患者腹腔积液具有显著的临床疗效。     

老年复发卵巢癌静脉联合腹腔热灌注化疗的疗效观察

目的分析老年卵巢癌老年复发卵巢癌静脉联合腹腔热灌注化疗疗效。方法 18例老年卵巢癌术后腹腔复发患者,行吉西他滨或多西他赛静脉化疗联合顺铂腹腔热灌注化疗4个周期。结果化疗结束后评价疗效,18例患者中完全缓解率(CR)2例,部分缓解率(PR)11例,稳定(SD)3例,进展(PD)2例,总有效率为72.2%,复发后1、2、3年生存率分别为72.2%、27.8%、5.6%。复发后中位生存时间为14.7个月,毒副作用主要表现为血液毒性及胃肠道反应,副作用小,安全有效。结论老年复发性卵巢癌患者,使用吉西他滨或多西他赛单药静脉化疗联合顺铂腹腔热灌注化疗具有多方面的优势,临床疗效明显,不良反应轻,耐受性好。     

深部热疗联合化疗治疗晚期卵巢癌的临床观察

目的观察并评价紫杉醇(T)联合腹腔热灌注顺铂(P)化疗治疗晚期卵巢癌的临床疗效。方法 42例均为初治的晚期患者,采用TP方案,P均经腹腔灌注给药后进行深部热疗1h,观察近期疗效及毒副反应。结果 32例腹水完全缓解26例(81.3%),42例病灶完全缓解28例(66.7%),42例患者总有效率100%。结论 TP方案双途径给药联合深部热疗治疗晚期卵巢癌疗效肯定,不增加毒副作用,值得临床推广应用。     

紫杉醇联合洛铂腹腔化疗治疗晚期卵巢癌恶性腹水疗效观察简

目的观察紫杉醇联合洛铂腹腔灌注化疗治疗晚期卵巢癌恶性腹水的疗效和不良反应。方法收集2010年3月-2012年12月32例晚期卵巢癌患者合并恶性腹水,给予紫杉醇联合洛铂腹腔化疗,紫杉醇135mg／m^2静滴,第1天;洛铂30mg／m^2腹腔灌注,第2天;每4周1疗程。完成2个疗程后评价疗效并观察不良反应。结果全组32例均可评价疗效和不良反应,完全缓解（CR）10例,缓解率31．3％,部分缓解（PR）20例,缓解率为62．5％,总有效率为93．8％。主要不良反应为骨髓抑制,消化道反应轻,未见肝肾功能损害等毒副反应,无治疗相关性死亡。结论紫杉醇联合洛铂腹腔化疗治疗晚期卵巢癌恶性腹水不良反应轻,在短时间内显著控制腹水,改善患者生存质量,值得临床进一步观察和应用。     

洛铂与顺铂腹腔灌注治疗恶性腹腔积液的对比研究

目的 对比研究洛铂灌注与顺铂灌注治疗恶性腹腔积液的疗效及安全性差异,总结最合理的治疗方案,促进预后.方法 随机抽取58例恶性腹腔积液病例资料,根据灌注药物不同分成洛铂组30例和顺铂组28例,其中洛铂30 mg/m2,顺铂60 mg/m2,治疗结束后评价近期疗效、生活质量评分及毒副反应情况.结果 两组生活质量评分及近期疗效比较差异无统计学意义(P＞0.05).洛铂组毒性反应发生率低于顺铂组(20.0％比28.6％),差异有统计学意义(P＜0.05).结论 ①无论是洛铂灌注抑或顺铂灌注,二者均能较好的控制恶性腹腔积液,总体疗效相当;②从药物安全性角度上评估,洛铂腹腔内灌注安全性更引人瞩目,毒副反应更少.     

草酸铂联合TNF腹腔内注射治疗胃肠道肿瘤所致腹水

目的：观察草酸铂（L-OHP）联合新型重组人肿瘤坏死因子（NrhTNF）腹腔内注射治疗恶性腹水的临床疗效、不良反应、对生存质量的影响。方法：20例晚期胃肠道肿瘤所致恶性腹水患者，（L-OHP）联合NrhTNF腹腔内注射，每周1次，连续2周。结果：20例患者无CR，PR55％（11／20），SD 35％（7／20）。主要不良反应为腹痛、发热、恶心，均较轻微。生活质量改善80％（16／20）。结论：（L-OHP）联合NrhTNF腹腔内注射治疗晚期胃肠道癌性腹水效果显著，不良反应轻微，可明显改善患者生存质量。     

Phase I trial of weekly cisplatin,irinotecan and paclitaxel in patients with advanced gastrointestinal cancer

Summary   Objectives: To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly cisplatin and irinotecan to treat advanced gastrointestinal malignancies. Methods: Thirty patients with metastatic or locally advanced (unresectable or recurrent) gastrointestinal solid tumors were enrolled on this single-center, phase I study. Patients were treated with paclitaxel given over 1h at 1 of 4 dose levels (40, 50, 65, or 80 mg/m²). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m²) and irinotecan (50 mg/m²). All treatment was administered sequentially, once a week, in 6-week cycles (4 weeks on, 2 weeks off). Dose-limiting toxicity (DLT) was defined as a 2-week delay in treatment for grade 3 or 4 non-hematologic toxicity, neutropenic fever, a 1-week delay for grade 4 hematologic toxicity, or a 2-week delay for grade 3 hematologic toxicity. Results: Thirty patients were recruited; 28 patients were assessable for safety. Most of the patients (70%) had no prior chemotherapy. The primary first-cycle DLTs were neutropenia, diarrhea, and nausea. Paclitaxel at 65 mg/m² was defined as the MTD. The most common grade 3–4 toxicities observed during all cycles were neutropenia (57%), febrile neutropenia (11%), diarrhea (29%), fatigue (29%), and nausea (18%). No patients had G-CSF (Neupogen, Amgen Inc., Thousand Oaks, CA) support. Responses were observed in gastric, esophageal, and pancreatic cancers. Conclusion: Paclitaxel at 65 mg/m², cisplatin (30 mg/m²), and irinotecan (50 mg/m²) given weekly can be safely administered to patients with solid tumor malignancies. To improve cumulative toxicities, a schedule modification was required (3-week cycle; 2-on, 1-off) Neutropenia was the most common DLT. This combination showed substantial activity, particularly in patients with gastric and esophageal adenocarcinoma, and phase II evaluation could be considered.     

The toxicity of cytarabine

The principal toxicity of standard induction regimens for acute non-lymphocytic leukemia (ANLL) [including cytarabine (ARA-C) 100 mg/m2 for 7 days plus an anthracycline] is myelotoxicity, leading to death in at least 25% of cases during induction in non-selected patients. The complete remission rate is less than 35% in patients over 65 years of age, due in part to an age-related increase of myelotoxicity. The other important adverse effect of standard-dose cytarabine is gastrointestinal toxicity, especially oral mucositis, diarrhoea, intestinal ulceration, ileus and subsequent Gram-negative septicaemia. Idiosyncratic reactions like exanthema, fever and elevation of hepatic enzymes are relatively frequent, but do not represent therapeutic problems. Intermittent high-dose cytarabine (3 g/m2 in 8 to 12 doses) is extremely myelosuppressive. Similarly, the gastrointestinal toxicity is formidable and dose-limiting. Severe, and sometimes irreversible, cerebellar/cerebral toxicity in 5 to 15% of courses of treatment limits the peak dose of cytarabine. The pathogenesis, prophylactic and therapeutic measures are unknown. These major toxicities are age-related and prohibitive to the use of high-dose cytarabine therapy in patients older than 55 to 60 years. Subacute noncardiogenic pulmonary oedema occurs in some patients, with an incidence of about 20%, and seems to have an intriguing coincidence with precedent streptococcal septicaemia; high-dose systemic steroids may be beneficial. Corneal toxicity is very frequent in high-dose cytarabine therapy but is always reversible. It is largely preventable with prophylactic steroid or 2-deoxycytidine eyedrops. Fever, exanthema and hepatic toxicity have an incidence similar to that in standard dosage. The maximum tolerable cumulated dose of cytarabine is significantly lower when the agent is administered as a continuous infusion, due to myelosuppression and gastrointestinal toxicity. Conversely, continuous infusion may be less neurotoxic. The antileukaemic effect of continuous infusion high-dose cytarabine is less well established. The only significant toxicity of low-dose cytarabine is myelosuppression. Given the generally poor condition of leukaemia patients, low-dose cytarabine therapy is well tolerated, although occasional cases of diarrhoea, reversible cerebellar symptoms, peritoneal and pericardial reactions, and ocular toxicity have been reported. Continuous infusion may be more toxic than the usual intermittent dosage. It is concluded that the toxicity of the standard induction regimen for ANLL is acceptable in patients younger than 60 to 65 years with no concurrent disease. Low dose cytarabine is tolerable for virtually all ANLL patients, but the overall therapeutic efficacy still needs to be defined and compared to standard therapy in the relevant age groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

重组人血管内皮抑制素联合全身化疗治疗晚期胃癌腹腔积液的临床观察

目的观察重组人血管内皮抑制素（恩度）联合化疗治疗晚期胃癌恶性腹腔积液的近期疗效,评价恩度局部应用的安全性和耐受性。方法对23例伴有恶性腹腔积液的晚期胃癌患者,应用恩度腹腔灌注给药,尽可能抽出腹腔内积液,注入恩度60rag,每周1次,连续3周。全身化疗静脉滴注奥沙利铂,按130mg／m^2计算给药,替吉奥80mg／（m^2·d）,分早晚2次餐后口服,连用14d,每3周为1周期。评价近期疗效、生活质量以及毒副反应。结果所有患者均可进行客观疗效评价及安全性评价,均完成2周期以上治疗,腹水控制有效率65％,其中5例完全缓解（CR）,10例部分缓解（PR）,5例稳定（sD）,3例进展（PD）,疾病控制率（DCR）为87％,生活质量改善患者有20例,占87％。药物相关性毒副反应不明显。结论恩度腹腔灌注给药能较好地控制恶性腹水,减轻临床症状,改善患者生活质量,安全性较好,不增加化疗药物的毒性。     

Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil,folinic acid and 3-weekly cisplatin for the treatment of patients with advanced gastric cancer

The aim of this study was to evaluate the toxicity and efficacy of combination chemotherapy with weekly 24-h continuous infusion of 5-fluorouracil (5-FU)/folinic acid, weekly paclitaxel and 3-weekly cisplatin in patients with unresectable, locally advanced or metastatic gastric adenocarcinoma. Between November 1999 and November 2001, 29 chemotherapy-naive patients (13 male and 16 female) with a median age of 56 years (range 22-72) were consecutively enrolled at three centers. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic acid 500 mg/m2 as a 2-h infusion. Paclitaxel 80 mg/m2 was administered as a 1-h infusion weekly and cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six weeks of therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was considered one cycle. A median of 3 cycles (range 1-5) was administered to 29 patients with a total of 73 cycles applied. All patients were assessable for toxicity and survival, 28 patients were assessable for response (one patient received less than one complete cycle and could not be evaluated for response). Four patients (14%) obtained a complete response and 10 patients (34%) a partial response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had stable disease. Seven patients (24%) had progressive disease during or within 4 weeks after treatment. The median progression-free and overall survival times were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall toxicity was acceptable. Hematological toxicity was favorable with only one patient (3%) experiencing WHO grade 3/4 leukocytopenia and one patient (3%) WHO grade 3/4 anemia. Non-hematologic WHO grade 3/4 toxicities included alopecia in 19 (66%), nausea/vomiting in six (21%), diarrhea in six (21%), neurotoxicity grade 3 in three (10%) and infection in three (10%) patients. A total of 42 applications (10%) (range 0-5) had to be postponed and dose reductions of at least one drug was necessary in 37% of applications. In three patients (10%) treatment was stopped because of toxicity. All patients were treated on an outpatient basis. Thus, the combination of weekly paclitaxel, cisplatin and continuously infused 5-FU/folinic acid appears to be a highly active regimen for the treatment of patients with advanced gastric cancer. Compared with our previous experience with the same combination of drugs but using paclitaxel at 175 mg/m2 given every 3 weeks, the protocol with weekly application of paclitaxel 80 mg/m2 shows a reduced incidence of hematologic toxicity, particularly leukopenia. Other organ toxicities apart from a slightly higher incidence of peripheral neuropathy were comparable between the two treatment protocols. Efficacy with a response rate of 50% was well preserved by this weekly regimen.     

Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer

Summary Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m² intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation.     

顺铂等药物灌注化疗和恩度治疗恶性胸腹腔积液的研究

目的观察顺铂等灌注和恩度治疗恶性胸腹积液的临床疗效及安全性。方法 62例晚期恶性胸腹水患者,治疗组32例,胸/腹腔内灌注恩度和化疗药物DDP/5-FU,对照组30例,仅灌注化疗药物DDP/5-FU,均3次/周,连续4周为一疗程,休息4周后,评价疗效及不良反应。结果治疗组中12例CR,16例PR,3例SD,1例PD,有效率为87.5%;对照组6例CR,13例PR,7例SD,4例PD,有效率为63.3%,两组比较差异有统计学意义（P〈0.05）,不良反应发生率两组比较无统计学意义（P〉0.05）。结论顺铂等加恩度灌注治疗恶性胸腹腔积液有较好的疗效和安全性,并有效提高了晚期肿瘤患者的生活质量,值得临床进一步推广应用。