顺铂胸腔灌注联合化疗治疗肺癌恶性胸水的疗效观察

目的:观察顺铂胸腔灌注联合静脉吉西他滨或培美曲塞化疗治疗非小细胞肺癌并恶性胸水的临床疗效。方法:41例非小细胞肺癌并恶性胸水患者,顺铂按75mg/m2胸腔灌注,同时行常规剂量的静脉吉西他滨或培美曲塞化疗,评价肺部肿瘤和胸水的控制情况、生活质量及不良反应。结果:17例肺鳞癌患者中,胸水治疗RR 76.5%,肺部肿瘤RR 29.4%,DCR 76.5%。24例肺非鳞癌患者中,胸水治疗RR 75%,肺部肿瘤RR 37.5%,DCR 83.3%。胸水治疗RR与肺部肿瘤DCR有相关性。90.2%患者生活质量获得改善。治疗不良反应轻。结论:顺铂胸腔灌注联合静脉吉西他滨或培美曲塞化疗治疗非小细胞肺癌并恶性胸水的临床疗效肯定,不良反应轻。     

香菇多糖联合顺铂治疗恶性胸腔积液

目的：观察香菇多糖联合顺铂胸腔灌注与单用顺铂治疗恶性胸腔积液的有效性和安全性。方法：收治恶性胸腔积液患者７３例,香菇多糖联合顺铂组（Ａ组）３８例,单用顺铂组（Ｂ组）３５例。用一次性中心静脉导管行胸腔置管和闭式引流胸液,Ａ组胸腔给药：香菇多糖４ｍｇ＋生理盐水２０ｍｌ,顺铂４０ｍｇ／ｍ２＋生理盐水５０ｍｌ;Ｂ组胸腔给药：顺铂４０ｍｇ／ｍ２＋生理盐水５０ｍｌ。结果：Ａ组患者总有效率和生活质量改善率均优于Ｂ组（Ｐ＜０.０５）,两组毒副反应相近。结论：胸腔闭式引流后灌注香菇多糖联用顺铂治疗恶性胸腔积液的疗效优于单用顺铂,且毒副反应轻微。     

力尔凡联合顺铂治疗恶性胸腔积液的临床观察

目的:观察力尔凡联合顺铂进行胸腔内注射治疗恶性胸腔积液的疗效和不良反应。方法:32例恶性胸腔积液病人,经B超定位行常规胸腔穿刺抽液术,尽量抽尽胸水后将力尔凡(30~40)mg 生理盐水30ml 顺铂60mg 地塞米松10mg缓慢注入患侧胸腔内,每周1次,一般2~4次。结果:CR10例,PR16例,NC6例,RR81.3%。所有病人在治疗过程中均未见明显发热及胃肠道反应,无明显肝肾功能损伤及心电图改变,有3例出现白细胞及血小板轻度减少。结论:力尔凡联合顺铂进行胸腔内注射治疗恶性胸腔积液是一种安全有效低毒的治疗方法,值得临床推广使用。     

Cisplatin in combination with irinotecan in the treatment of patients with malignant pleural mesothelioma: a pilot phase II clinical trial and pharmacokinetic profile.

BACKGROUND: The purpose of this study was to assess the efficacy and toxicity of a combination of cisplatin and irinotecan (CPT-11) in the treatment of patients with malignant pleural mesothelioma and to characterize the pharmacokinetic profiles of CPT-11 and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). METHODS: Fifteen previously untreated patients with malignant pleural mesothelioma were treated with cisplatin (60 mg/m2 on Day 1) and CPT-11 (60 mg/m2 on Days 1, 8, and 15) administered intravenously and followed by a 1-week rest period. The course of treatment was repeated every 28 days. After intravenous administration, the levels of CPT-11 and SN-38 in the plasma and pleural fluid were determined for each histologic subtype of mesothelioma. RESULTS: All patients were evaluable for response and toxicity. Four partial responses (response rate of 26.7%) with a median response duration of 25.9 weeks and 2 regressions of evaluable disease (overall response rate of 40%) were observed. The median survival time after chemotherapy was 28.3 weeks, and the median time to treatment failure was 22.1 weeks. The 1-year survival rate for all patients was 38.5%. Toxicity was well tolerated, and there were no treatment-related deaths. World Health Organization Grade 3 leukopenia occurred in 3 patients (20%), and Grade 1 or 2 diarrhea occurred in 3 patients (20%). There was no excess toxicity in patients with large pleural effusions compared with those with no pleural effusions. CPT-11 and SN-38 were detected in the pleural fluid 1 hour after intravenous administration. The maximum concentrations of CPT-11 and SN-38 in the pleural fluid were 36.5% and 75.8%, respectively, of the corresponding plasma values. CONCLUSIONS: The combination of cisplatin and CPT-11 had definite activity against malignant pleural mesothelioma and was well tolerated. The intravenous administration of CPT-11 produced adequate distribution of CPT-11 and its active metabolite SN-38 into the pleural fluid and allowed a higher concentration of the more active SN-38 to make contact with mesothelioma cells in the thoracic cavity. These results warrant further clinical evaluation of this combination chemotherapy for the treatment of malignant pleural mesothelioma in a confirmatory Phase II trial.     

Intrathoracic infusion with a combination of low-dose minocycline, OK-432 and cisplatin for malignant pleural effusion

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.     

热灌注化疗治疗恶性胸水30例临床观察

目的：观察体外高频热疗联合胸腔热灌注化疗治疗恶性胸水的疗效及不良反应。方法：恶性胸水60例,同期分为治疗组及对照组各30例。胸腔穿刺行闭式引流干净胸水后,治疗组给予43℃-45℃的生理盐水1000ml＋顺铂50mg/m2,以HGG2-102体腔热灌注治疗机灌注入胸腔,使进入胸腔的液体温度维持在41℃-43℃;灌注结束后,采用高频热疗机行胸腔局部热疗41℃-43℃,60分钟,每周热疗2次;对照组给予生理盐水1000ml＋顺铂50mg/m2胸腔内注入。两组均每周灌注1次,连续灌注3周,评定疗效。结果：治疗组有效率83.3%,KPS评分升高率63.3%;对照组有效率45.5%,KPS评分升高率31.8%。治疗组胸水控制率、KPS升高率均较对照组明显为优（P〈0.05）。两组不良反应无明显差异。结论：体外高频热疗联合胸腔热灌注化疗治疗恶性胸水疗效好,可以耐受。     

氟尿嘧啶联合丝裂霉素胸腔注射治疗高龄恶性胸腔积液

目的探讨氟尿嘧啶(5-Fu)联合丝裂霉素(MMC)胸腔注射治疗高龄恶性胸腔积液的疗效.方法病理确诊的肺癌伴恶性胸腔积液高龄患者37例,随机分为治疗组(20例)和对照组(17例).治疗组胸腔内注射5-Fu 750 mg/m2,MMC 8 mg/m2;对照组胸腔内注射顺铂(DDP)40 mg/m2,每3～5天一次,共3～5次.观察疗效、毒副反应及生活质量.结果治疗组总有效率为75.0%,对照组为70.6%,差异无显著性(P>0.05).治疗组骨髓抑制、胃肠反应明显低于对照组(P<0.05).治疗组Karnofsky评分>60分者较对照组显著提高(P<0.05),<50分者较对照组明显下降(P<0.05).结论 5-Fu联合MMC胸腔注射治疗老年恶性胸腔积液是一种安全性高、毒副反应小、耐受性好的有效方法.     

Response and pharmacokinetics of cisplatin instilled into the pleural cavity

The response and pharmacokinetics of cisplatin instilled into the pleural cavity were studied in 11 patients with malignant pleural effusion; 10 patients had primary lung cancer and one had breast cancer. All of them were adenocarcinoma histologically. In five of the 11 patients effusion disappeared and its cytology became negative for malignancy after four weeks. In the other six patients effusion was reduced and its cytology became negative for malignancy after four weeks. Toxicity was almost similar to that in systemic administration of cisplatin but a few patients had chest pain and fever possibly due to local irritation. The pharmacokinetics showed that a high concentration of cisplatin (free-form, 48.9 micrograms/ml) was maintained over a long period (free from (t 1/2) beta = 33.6 hours) in the pleural cavity. This was regarded as the reason for the high response to this therapy. The intrapleural instillation of cisplatin into the pleural cavity therefore seems to be an effective modality for malignant pleural effusion.     

华蟾素联合顺铂腔内注射治疗恶性胸腹水

目的：探讨华蟾素联合顺铂腔内注射治疗恶性胸腹水的疗效。方法：将66例恶性胸腹水患者随机分为2组，试验组33例抽取胸腹水后腔内灌注华蟾素20mL和顺铂60mg，每周1次，连续2—4周。对照组33例采用单药顺铂60mg腔内灌注。结果：试验组22例恶性胸水患者治疗有效率86．4％；11例恶性腹水患者治疗有效率72．7％；试验组治疗恶性胸腹水总有效率81．8％，KPS评分提高21例，稳定10例，降低2例。对照组21例恶性胸水患者的有效率为52．4％；12例恶性腹水患者的有效率为41．7％；对照组治疗恶性胸腹水总有效率为48．5％，KPS评分提高9例，稳定12例，降低12例。2组疗效比较，试验组优于对照组（P〈0．05），毒性反应更小（P〈0．05）。结论：华蟾素联合顺铂腔内注射治疗恶性胸腹水疗效满意，副作用小，值得临床推广应用。     

双途径联合化疗肺癌胸腔积液的疗效观察

目的　观察应用双途径联合化疗治疗恶性胸腔积液的临床疗效。方法　将 3 9例肺癌恶性胸腔积液患者随机分成 2组 ,治疗组 19例 ,采用PICC管 (外周穿刺中心静脉导管 )行胸腔闭式引流 ,8～ 48h内引流近乎消失后注入DDP 60～ 80mg ,术后d1～ 5予EP或NP方案化疗 1个周期 ,4周重复 ;对照组 2 0例 ,采用胸腔抽液 ,腔内注入DDP 60～ 80mg化疗 ,d4～ 9后重复 1次。结果　治疗组CR3 1 6% ( 6/19) ,有效率为 84 2 % ( 16/19) ;对照组CR 15 % ( 3 /2 0 ) ,有效率为 5 5 % ( 11/2 0 )。结论　双途径联合化疗治疗恶性胸腔积液疗效满意 ,安全、可靠 ,值得临床推广应用     

胸腔置管引流灌注高聚生治疗恶性胸水40例临床观察

目的：观察高聚生联合化疗药物胸腔内灌注对恶性胸水的疗效。方法：采用胸腔穿刺、置入长套管针灌注高聚生及顺铂与单用顺铁疗效对照。结果：高聚生＋顺铂组４０例,有效率８２．５％;化疗组顺铂３６例,有效率４７．２％（ｐ〈０．０５）。结论：经长套管针置入灌注生物制剂＋化疗药物,疗效明显优于胸腔内单纯灌注化疗药物,因此生物制剂高聚生经长套管针置入胸腔内灌注不失为治疗恶性胸水的有效方法之了。     

甘露聚糖肽联合顺铂胸腔内灌注治疗恶性胸腔积液的临床观察

目的:评价甘露聚糖肽联合顺铂胸腔内灌注治疗恶性胸腔积液的临床疗效及毒副反应。方法:60例恶性胸腔积液患者随机分为两组。所有患者均在经中心静脉导管胸腔持续闭式引流后灌注治疗,治疗组（31例）:甘露聚糖肽80-100mg,顺铂60mg胸腔内灌注;对照组（29例）:单用顺铂60mg胸腔内灌注。上述治疗每周2次,连续1-2周。结果:治疗组总有效率为83.9%（26/31）,明显优于对照组的58.6%（17/29）,差异有显著意义（P<0.05）。治疗组生活质量改善率为71.0%,也显著高于对照组的44.8%（P<0.05）。毒副反应主要为轻度消化道反应、白细胞降低及发热、胸痛。结论:甘露聚糖肽联合顺铂治疗恶性胸腔积液有良好的协同作用,能改善生活质量,毒副反应轻,值得临床广泛应用。     

热疗联合胸腔置管化疗治疗恶性胸腔积液临床研究

目的观察热疗联合胸腔置管化疗治疗恶性胸腔积液的临床疗效及其毒副反应。方法62例恶性胸腔积液患者随机分为射频热疗联合胸腔置管化疗组(治疗组)和单纯胸腔置管化疗组(对照组)各31例。对照组先行胸腔闭式引流后,将顺铂60 mg、氟尿嘧啶1.0 g、吡喃阿霉素40 mg各加生理盐水50 ml胸腔内注射,再将地塞米松20 mg胸腔内注射后夹管,每周1次,灌注2次后拔管观察,治疗组于胸腔注射药物后行热疗,当周再行1次单纯热疗,一疗程4次。结果对照组胸腔积液控制有效率为54.8%,治疗组为83.9%,两组差异有显著性(P<0.05)。对照组生活质量改善率为48.4%,治疗组为77.4%,两组差异有显著性(P<0.05)。两组化疗毒副反应发生率差异无显著性。与热疗相关的毒副反应为局部皮肤疼痛4例(13.0%),皮下脂肪硬结3例(9.7%)。结论热疗联合胸腔置管化疗治疗恶性胸腔积液是一种安全可靠、高效低毒的治疗方法,值得临床推广使用。     

胸腔内灌注化疗癌性胸水

目的探讨胸腔内准注化疗治疗癌性胸水的临床效果。方法对56例癌性胸水患者（其中原发肿瘤为肺癌32例,乳癌17例,胃癌3例,大肠癌2例,恶性胸膜间皮瘤2例采用针吸法和胸腔内置管引流法使恶性胸水大部分排出。胸腔内注入化疗药：DDP70—100mg,ADM50-70mg,MMC15-20mg,5-Fu1000-1500mg。结果本组总有效率96.4％。随访时间均超过12个月。胸水缓解期超过6个月以上者为73.2％（41／56）。毒性反应食欲减退、恶心、呕吐者占72％,白细胞、血小板降低者19.8％。结论胸腔内灌注化疗治疗癌性胸水具有疗效好、毒性低、费用少、是值得推广的治疗方法。     

局部胸腔灌注化疗联合全身化疗对肺腺癌合并恶性胸腔积液的疗效

目的 探讨局部胸腔灌注化疗联合全身化疗对肺腺癌合并恶性胸腔积液的疗效.方法 回顾性分析85例肺腺癌合并恶性胸腔积液患者的临床资料,根据治疗方法不同将患者分为局部组(n=38)和联合组(n=47).局部组将顺铂+白细胞介素-2经胸腔置管引流后注入胸腔,联合组在局部组的基础上辅以培美曲塞全身化疗.比较两组患者恶性胸腔积液的治疗效果、治疗前后KPS评分变化以及治疗后的不良反应发生率.结果 联合组患者恶性胸腔积液的治疗有效率为93.62%,明显高于局部组的44.74%(P﹤0.01);联合组患者KPS评分改善有效率为80.85%,高于局部组的44.74%(P﹤0.05).两组患者的各种不良反应发生率比较,差异均无统计学意义(P﹥0.05).但联合组中个别患者出现白细胞减少、胸痛及胃肠道反应等3级不良反应,需及时对症治疗.结论 在顺铂+白细胞介素-2胸腔灌注化疗的基础上辅以培美曲塞全身化疗,可有效治疗肺腺癌合并恶性胸腔积液,值得临床推广.     

高频热疗联合腔内化疗治疗藏族恶性胸腔积液患者的临床观察

目的：观察高频热疗联合腔内化疗治疗藏族恶性胸腔积液患者的疗效和毒副反应。方法57例藏族恶性胸腔积液患者随机分为2组,尽可能排尽胸腔积液后,治疗组29例患者给予顺铂胸腔内灌注,然后进行高频热疗;对照组28例患者只给予顺铂胸腔内灌注。结果治疗组总有效率为86.21%,高于对照组的57.14%（χ2=5.532,P=0.019）。治疗组生活质量改善明显优于对照组（χ2=6.339,P=0.042）。结论热疗高频热疗联合腔内化疗对恶性胸腔积液疗效确切,安全性高。     

A case of remission induced in diffuse pleural malignant mesothelioma by the treatment with cisplatin and doxorubicin

A 66-year-old male patient with diffuse pleural malignant mesothelioma was successfully treated with cisplatin and doxorubicin. He was admitted to our hospital because of massive pleural effusion. The diagnosis was made by pleural needle biopsy. He received 100 mg of cisplatin and 50 mg of doxorubicin every 5 weeks. Regression of the tumor and decrease of pleural effusion were observed after the treatment. A partial remission of 10 months duration was achieved. Cisplatin and doxorubicin were thought to be the most active cytotoxic agents in the treatment of malignant mesothelioma.     

凝血酶联合顺铂治疗恶性血性胸水

[目的]观察凝血酶联合顺铂治疗恶性血性胸水的疗效.[方法]恶性血性胸水患者46例经胸穿或闭式引流尽量排净胸水,治疗组(23例)向胸腔内注入凝血酶 顺铂,对照组(23例)单纯顺铂胸腔内注入,4周后评价疗效.[结果]治疗组有效率86.9%,对照组有效率仅52.2%(P《0.05).治疗组的KPS评分改善率(78.3%)高于对照组(34.8%),两者差异有显著性(P《0.01).毒副反应均较轻,无需特殊处理.[结论]凝血酶联合顺铂治疗恶性血性胸水疗效较好,而且副反应轻,可安全用于临床.     

Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. Pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions. In contrast to this approach, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion. Intracavitary cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma. There has been little previous experience, however, with intrapleural cisplatin-based chemotherapy. As part of a planned series of trials in malignant mesothelioma, the Lung Cancer Study Group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. From April 1986 to November 1987, 46 patients with cytologically proven, symptomatic, and previously untreated malignant pleural effusions were entered on study. A single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest tube, which was then immediately removed. Patients were evaluated for toxicity and response at 24 hours; 1, 2, and 3 weeks; and then monthly. No recurrence of the effusion was considered a complete response (CR). Partial response (PR) was defined as a 75% or greater decrease in the amount of the effusion on serial chest radiographs. One patient experienced reversible grade 4 renal toxicity, four patients had grade 3 hematologic toxicity, and five patients had grade 3 cardiopulmonary toxicity. The overall response rate (CR plus PR) at 3 weeks was 49% (18 of 37 patients). The median length of response was 9 months for a CR and 5.1 months for a PR. The outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma.     

Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.

PURPOSE: Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS: Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half-lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS: Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS: The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels.