沙培林联合羟基喜树碱腔内给药治疗恶性胸腔积液

目的：为观察沙培林联合羟基喜树碱腔内给药治疗恶腔积液患的治疗。方法：60例恶性胸腔积液患采用胸腔穿刺，使用比利时生产的贝朗可分裂中心静脉导管置入胸腔、接负压瓶持续闭式引流排胸液。并随机分成两组，治疗组采用沙培林联合羟基喜树碱治疗（30例），第一周2次，每隔3天一次，由引流管注入生理盐40ml加羟基喜树碱30mg，第2周连续3天注入沙培林5KE/次、10KE/次、10KE/次，对照组单用羟基喜树碱治疗（30例），每一周2次，每隔3天一次，由引流管注入生理盐水40ml加羟基喜树碱30mg。结果：治疗组有效率90%[CR11例（37%） PR16例（53%）]，对照组有效率67%[CR8例（27%） PR12例（40例）]。经论：沙培林联合羟基喜树碱腔内注射治疗恶性胸腔积液优于单用羟基喜树碱，而胸腔穿刺置管引流创伤轻微，无倒流污染，引流通畅彻底，避免胸膜多房性包裹粘连的形成以至带来后续治疗困难，可防止医源性感染及气胸等并发症。     

沙培林治疗36例恶性胸腔积液临床疗效观察

目的：观察沙培林治疗恶性胸腔积液的临床疗效。方法：经B超定位并行胸穿抽取胸腔积液，2周内隔日1次注入不同剂量的沙培林。结果：36例患者有效率91.7%，中位缓解期8.5个月。中位生存期11个月。主要毒副反应为不同程度发热。结论：沙培林能有效治疗恶性胸腔积液。     

经胸导管注入羟基喜树碱联合白细胞介素-2治疗恶性胸腔积液52例

 目的　分析胸腔内留置静脉导管注入羟基喜树碱及白细胞介素-2（IL-2）与单纯注入羟基喜树碱治疗恶性胸腔积液的临床疗效及患者不良反应。方法　100例经病理组织学或细胞学确诊的恶性胸腔积液患者,随机分为两组（两组均采用中心静脉导管置入胸腔并保留,在胸腔积液引流干净后）治疗组52例,由导管交替注入羟基喜树碱和IL-2;对照组48例,由导管注入羟基喜树碱。注药后两组均夹管5 d后再引流,无积液引出后再注入上述药物,夹管保留5 d,一般注药2～4次。未行全身化疗,4～6周后复查B型超声、胸部CT,进行疗效评价。结果　治疗组有效率88.5 %（46／52）;对照组有效率62.5 %（30／48）,差异有统计学意义（P＜0.05）;两组不良反应均较轻微,差异无统计学意义（P＞0.05）。结论　羟基喜树碱联合IL-2胸腔内注入治疗恶性胸腔积液有效率较高且不良反应轻微,值得进一步推广应用。     

沙培林治疗36例恶性胸腔积液临床疗效观察

目的 :观察沙培林治疗恶性胸腔积液的临床疗效。方法 :经B超定位并行胸穿抽取胸腔积液 ,2周内隔日 1次注入不同剂量的沙培林。结果 :36例患者有效率 91 7% ,中位缓解期 8 5个月 ,中位生存期 11个月。主要毒副反应为不同程度发热。结论 :沙培林能有效治疗恶性胸腔积液     

羟基喜树碱(拓僖)联合高聚生治疗恶性难治性胸腔积液

目的:观察应用羟基喜树碱联合高聚生治疗恶性、难治性胸腔积液的疗效.方法:对临床治疗中效果较差的中、大量恶性胸腔积液及既往治疗无效的恶性胸腔积液患者66例(治疗组36例,对照组30例)进行治疗,全部患者均经PICC管(外周穿刺中心静脉导管)行胸腔闭式引流,1～3天引流至胸水近乎消失后注入药物.治疗组羟基喜树碱(拓僖)30mg,高聚生2000～3 000U胸腔注射,地塞米松5mg肌肉注射;对照组顺铂60～70mg,地塞米松10mg胸腔注射,胃复安20mg肌注.结果:治疗组CR 44.4%(16/36),有效率为86.1%(31/36).对照组CR 26.7%(8/30),有效率为63.3%(19/30).结论:羟基喜树碱联合高聚生治疗恶性难活性胸腔积液疗效满意,不良反应轻微,尤其对大量血性胸腔积液及既往治疗无效者效果良好,安全、可靠,值得临床广泛应用.     

沙培林治疗恶性胸腔积液的临床研究

观察沙培林治疗恶性胸腔积液的疗效及副作用。对30例恶性胸腔积液患者应用沙培林腔内给药治疗，B超检查，观察效果。有效率达66．7％，不良反应主要是胸痛和发热。沙培林是治疗恶性胸腔积液的有效药物之一。     

沙培林联合丝裂霉素一次性治疗恶性胸腔积液

目的本文观察了沙培林(OK-432)联合丝裂霉素一次性用药治疗恶性胸腔积液的疗效、不良反应及并发症.方法首先最大限度地排净胸水,然后将丝裂霉素10 mg NS 10 ml,沙培林20 KE NS 20 ml,地塞米松5 mg NS 10 ml,2%利多卡因10 ml分别注入胸膜腔,48 h后再尽量抽尽残留胸水后拨管.结果48例恶性胸腔积液患者中,显效12例,部分有效32例,总有效率91.7%.主要不良反应为发热、胸痛、一过性血白细胞升高.3例发生漏入性气胸,2例发生复张性肺水肿.结论沙培林(OK-432)联合丝裂霉素一次性用药治疗恶性胸腔积液疗效肯定,不良反应可以耐受.     

尿激酶联合沙培林治疗多房性包裹性恶性胸腔积液

目的观察尿激酶联合沙培林治疗多房性包裹性恶性胸腔积液的临床效果及安全性。方法收集21例患有多房性包裹性恶性胸腔积液的患者,先经皮穿刺中心静脉导管胸腔置管引流,然后经导管注入尿激酶25万U后夹管4h以上后再次引流,共注药3～5次;待胸水基本引尽、肺复张后经导管注入沙培林10KE,去枕平卧后每10～15min转动体位,共翻身3圈,24h后再次引流,共注药2～3次。结果所有患者胸腔注入尿激酶后均能使胸水通畅、肺复张完全,有效率为100%。有5例（23.8%）患者出现一过性血性胸水颜色加深或原为非血性胸水变为血性胸水,无全身出血,有1例（4.8%）出现中度发热,治疗后1d热退。继而用沙培林后完全缓解（CR）16例（76.2%）,部分缓解（PR）3例（14.3%）,无效（NC）2例（9.5%）,胸水控制总有效率为90.5%,有14例（66.7%）出现低到中度发热,持续时间为2～10d,有5例（23.8%）出现轻度的胸痛,用新广片或吲哚美辛栓剂可控制。结论尿激酶联合沙培林治疗多房性包裹性恶性胸腔积液效果明显,不良反应轻微,值得临床推广应用。     

沙培林治疗恶性胸腔积液的临床研究

观察沙培林治疗恶性胸腔积液的疗效及副作用。对 30例恶性胸腔积液患者应用沙培林腔内给药治疗 ,B超检查 ,观察效果。有效率达 66 7% ,不良反应主要是胸痛和发热。沙培林是治疗恶性胸腔积液的有效药物之一。     

沙培林与顺铂治疗恶性心包积液的近期疗效

［目的］观察沙培林(OK-４３２)及顺铂治疗恶性心包积液的近期疗效和耐受性。［方法］５６例中等及大量恶性心包积液患者心包穿刺置管引流后腔内随机分组注射，沙培林组(生理盐水２０ml＋OK-４３２２KE＋地塞米松１０mg／次)３０例，顺铂组(生理盐水４０ml＋顺铂５０mg～６０mg／次)２６例，腔内用药最多重复３次。［结果］沙培林组有效率为９３．３％。主要不良反应为发热；顺铂组有效率为６５．４％，主要不良反应为骨髓抑制及胃肠道反应，两组有效率及不良反应均有显著差异(P＜０．０５)。［结论］沙培林治疗恶性心包积液沙培林有效率高，不良反应小，患者耐受性好，值得临床推广应用。     

Comparison of intrapleural OK-432 and cisplatin for malignant pleural effusion in lung cancer patients

Malignant pleural effusion is typical of complications in advanced lung cancer patients, most of whom complain of dyspnea. The standard treatment for symptomatic pleural effusion is intrapleural administration of a chemical agent. In Japan, OK-432, a streptococcal preparation, and cisplatin (CDDP) have been among the most frequently used chemical agents. There have been very few reports on the efficacy of chemical agents for malignant pleural effusion. We compared therapeutic efficacy and toxicity of intrapleural OK-432 with CDDP in a case-control study. The subjects consisted of 32 lung cancer patients with malignant pleural effusion who were admitted to our hospital between January 2000 and June 2004. The therapeutic efficacy was assessed from duration of chest drainage after intrapleural administration, response rate, time to progression of malignant pleural effusion, and survival time. No statistically significant difference was observed for therapeutic efficacy. Although the OK-432-treated group had only grade 1 fever, chest pain, nausea, the CDDP-treated group had a grade 2 increase in creatinine and grade 3 nausea. Intrapleural OK-432 seemed to be better tolerated in the treatment of malignant pleural effusion than intrapleural CDDP.     

Epidermal growth factor receptor in breast cancer: Correlation of quantitative immunocytochemical assays to prognostic factors

Summary Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively. The patients received their first thoracentesis between 1980 and 1990. Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2. Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1). Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p < 0.01). Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p< 0.001) difference in survival. Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p < 0.005) factor to prolong the survival of the patients among several prognostic factors. Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.     

Comparison of OK-432 and mitomycin C pleurodesis for malignant pleural effusion caused by lung cancer. A randomized trial.

A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK-432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer.     

顺铂联合甘露聚糖肽与联合OK-432胸腔注射治疗恶性胸腔积液的临床分析

[目的]对比观察中心静脉导管胸腔引流并顺铂联合甘露聚糖肽（多抗）或OK-432（沙培林）治疗恶性胸腔积液的临床疗效和毒副反应。[方法]99例恶性胸腔积液病人，随机分为2组：甘露聚糖肽组（A组）53例，OK432组（B组）46例。行中心静脉导管胸腔引流术，A组胸腔注射甘露聚糖肽和顺铂，B组胸腔注射0K432和顺铂。两组均每周重复，连续2～4周。[结果]A组RR43例（81．1％）。B组RR39例（84．8％），两组有效率无统计学差异（P=0．631）。A组有3例（5．7％）病人发热，B组有24例（52．2％）病人发热（P〈0．001）。[结论]中心静脉导管胸腔引流并顺铂联合甘露聚糖肽或OK432治疗恶性胸腔积液均较安全且方便，临床疗效相似，但沙培林组发热的发生率远高于甘露聚糖肽组。     

Pleuritis carcinomatosa

The most used standard therapy for malignant pleural effusion(MPE)is tube thoracostomy drainage, except in cases where there are few pleural effusions or no symptoms. It has been reported that instilling an intrapleural agent is necessary for producing pleurodesis after tube thoracostomy drainage. To date, numerous chemical agents for the treatment of MPE have been studied. These include antibiotics, antineoplastic agents, biological response modifiers and others, that showed various degrees of chemical sclerosis. It was entered on a randomized comparison of tetracycline and bleomycin for treatment of MPE. The rate and time to recurrence were both significantly greater with bleomycin. In comparison, Talc was superior to bleomycin for control of MPE. Therefore, thoracoscopic pleurodesis with talc is now considered to be the gold standard treatment for MPE. However, talc has not been commercially available in Japan. We sought to evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin, OK-432 or cisplatin plus etoposide(PE), for the management of malignant pleural effusion in previously untreated non-small cell lung cancer. The primary endpoint, pleural progression-free survival did not differ significantly between groups. Intrapleural treatment using OK-432 in the management of MPE was selected because it had the highest 4-week pleural progression-free survival rate and toxicity was tolerable. At present, OK- 432 is the standard agent used in Japan.     

Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515

To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes) or cisplatin plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1mg/kg (maximum 60mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10KE/body), or the PE arm: cisplatin (80mg/m(2)) and etoposide (80mg/m(2)). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3-4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.     

Clinical evaluation of intrapleural or peritoneal administration of lentinan and OK-432 for malignant effusion

It is very important to control the Th2-dominant condition in cancer patients while they are undergoing immunotherapy. OK-432 powerfully guides Th1 cytokine, but sometimes it can not eliminate the Th2 dominant state in cancer patients, which is needed to induce Th2 cytokine. Premedication with combined LTN and OK-432 is an effective therapy for controlling the Th1/Th2 balance. We tried administering LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 9 lesions of the 8 cases, 6 showed complete remission and 1 showed partial response. The level of IL-12 (p70) and IFN-gamma in the pleural effusion or ascites of the combination group was higher than the OK-432 only group. In conclusion, LTN and OK-432 combined therapy appears to be an effective local treatment.     

Clinical evaluation of intrapleural or peritoneal repetitive administration of Lentinan and OK-432 for malignant effusion

LTN and OK-432 combined therapy is effective for controlling Th1/Th2 balance. We tried a repetitive administration of LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 11 lesions of the 10 cases, 7 revealed complete remission and 1 revealed partial response. The level of IL-12 (p70) and IFN-gamma in ascites of two gastric cancer patients after the second administration of LTN and OK-432 was much higher than those after the first administration, whereas the level of IL-10 was not suppressed strongly. In 8 lesions that we could confirm complete remission or partial response, 7 lesions were improved after two or three administrations of LTN and OK-432. In conclusion, a repetitive intracavital administration of LTN and OK-432 is effective for malignant effusion.