Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) to patients with peritoneal carcinomatosis

The pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal perfusion (CHPP) was characterized in patients with peritoneal carcinomatosis. Cisplatin was added into the perfusate with escalating doses from 100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees C after a tumor debulking procedure. Samples of both the perfusate and blood were obtained during the perfusion and 30 minutes after the perfusion. Cisplatin plasma and perfusate concentrations were determined by flameless atomic absorption spectrometry with a lower limit of detection of 2 ng/ml and a coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the completion of perfusion was 27.8% +/- 20% of the total dose. The maximum cisplatin concentrations in the perfusate were 10 times higher than those in plasma. The area under the concentration-time curve (AUC) of the perfusate was 13 times higher than the AUC of plasma. A two-compartment model with an additional peritoneal cavity compartment fits to the data best based on the Akaike information criterion. However, the interpatient variability was considerably high (CV < 100%). In conclusion, cisplatin administered by hyperthermic peritoneal perfusion resulted in a pharmacological advantage by obtaining higher and direct drug exposure to the tumor in the peritoneal cavity while limiting systemic absorption and toxicity. Using a complex two-compartment model, the authors were able to characterize the pharmacokinetics of cisplatin given intraperitoneally via this technique.     

Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis

Purpose

Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin’s systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.

Methods

Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m²,doxorubicin 15 mg/m²) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).

Results

The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0–90 min of 2.87 mM·min and estimated 0–60 min of 2.45 mM·min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.

Conclusions

Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate.     

Penetration of carumonam into the pleural fluid: comparison of intravenous bolus and constant infusion in rats with experimentally induced pleurisy

The penetration of carumonam into the pleural exudate of rats was compared after intravenous administration of 30 mg kg(-1) of the drug as a bolus dose or by continuous infusion over 60 min. Both methods of administration ensured a good penetration of carumonam in pleural exudate, as measured by the areas under the concentration-time curves (AUC). The mean values of the ratio of AUC in exudate to AUC in serum (1.07 +/- 0.11 and 0.96 +/- 0.13 for bolus injection and continuous infusion, respectively) were not significantly different. Administration as a bolus dose resulted in significantly higher peak concentrations in pleural exudate as well as in shorter peak times, whereas continuous infusion produced carumonam levels above the MIC for consistently longer times. The pharmacokinetic parameters obtained by analysis of serum carumonam concentrations proved to be independent of the mode of administration. The foregoing results suggest that carumonam may constitute an effective therapeutic alternative to existing antibiotics for the treatment of pleurisy caused by susceptible organisms. No clear superiority of either method of administration could be established on the basis of pharmacokinetic data.     

Comparative pharmacokinetics of tetrahydropyranyl-doxorubicin and doxorubicin in rat isolated lung.

Rat isolated perfused lungs (Sprague-Dawley rats, n = 20) were studied to compare the pulmonary uptake of a new anthracycline, tetrahydropyranyl-doxorubicin (THP-DXR) with that of doxorubicin (DXR). Lung perfusions were initiated with a constituted medium containing either drug at concentrations of 1, 10 or 100 microM. Lungs were perfused by recirculation for 60 min. Thirteen perfusate samples were collected over 60 min and subjected to HPLC for assay. The perfusate concentration of THP-DXR decreased to 24 +/- 5% of the initial concentration and to 8 +/- 2%, 20 and 60 min after the beginning of the infusion, respectively. Corresponding values for DXR were 77 +/- 16 and 52 +/- 15%, respectively (P less than 0.05). During the THP-DXR perfusion, the area under the perfusate concentration vs time curve (AUC) was decreased to one-third and the clearance was increased 3-fold (P less than 0.05). The pulmonary concentration of THP-DXR reached 0.032 +/- 0.01 mumol g-1 60 min after the beginning of a perfusion of 1 microM of the drug. This concentration increased to 0.379 +/- 0.11 mumol g-1 when the initial dose concentration was 10 microM. Corresponding lung concentrations for DXR were 0.013 +/- 0.001 and 0.150 +/- 0.04 mumol g-1, respectively (P less than 0.05). The perfusate concentration/initial concentration ratio decreased by the same amount whether a 1 or 10 microM initial concentration of either drug was used. An initial concentration of 100 microM of THP-DXR, unlike DXR, consistently induced oedema in the perfused lung. No metabolite of either drug was revealed during the course of our study.(ABSTRACT TRUNCATED AT 250 WORDS)     

顺铂和香菇多糖胸腔内注射治疗老年肺癌伴胸腔积液

目的观察胸腔内置管注入顺铂和香菇多糖治疗老年肺癌伴胸腔积液的疗效。方法肺癌性胸腔积液老年(70-87岁)患者120例,随机均分为顺铂组(A组)、香菇多糖组(B组)和顺铂+香菇多糖组(C组)。经皮胸腔内置管引流尽胸液后,向胸腔内注药,观察治疗效果。结果总有效率:A组55.0%,B组52.5%,C组77.5%;C组总有效率高于A组和B组(P<0.05)。结论顺铂联合香菇多糖胸腔内注射治疗老年肺癌性胸腔积液疗效好,不良反应少。     

内生场热疗联合胸腔内注药治疗恶性胸腔积液的疗效观察

目的观察内生场热疗联合胸腔内注入香菇多糖和顺铂治疗恶性胸腔积液的近期疗效和安全性。方法57例恶性胸腔积液患者随机分为观察组和对照组;所有患者均采用中心静脉导管胸腔穿刺置管闭式引流,对照组将香菇多糖和顺铂用生理盐水稀释后分别注入胸腔内进行治疗,每周1-2次,共3～4周;观察组在对照组基础上加用内生场热疗,每周2次,共3～4周。结果观察组胸腔积液完全缓解率为34．5％（10／29）,部分缓解率为55．2％（16／29）,总有效率为89．7％;对照组胸腔积液完全缓解率为21．4％（6／28）,部分缓解率为46．4％（13／28）,总有效率为67．9％。经统计学处理两组比较差异有显著性（P〈0．05）。结论内生场热疗联合香菇多糖和顺铂胸腔内注药能够提高恶性胸腔积液治疗的有效率,并能改善生活质量,优于单纯胸腔注药治疗。     

化疗联合深部热疗治疗肺癌恶性胸腔积液的临床研究

目的探讨化疗联合深部热疗治疗肺癌恶性胸腔积液的临床疗效。方法收集我院近期收治住院的恶性胸腔积液患者86例,遵照知情同意原则分为两组,对照组40例行胸腔内灌注顺铂（DDP）化疗,实验组46例联合深部热疗,对比两组患者的临床疗效及并发症发生情况。结果实验组患者的总有效率为97．8％,高于对照组的85．0％（P〈0．05）,且实验组患者的胸液消失时间、胸膜增厚度、包裹性脓胸、胸膜反应均优于对照组（P〈0．05）。结论运用化疗联合深部热疗治疗肺癌恶性胸腔积液,可使患者的临床疗效得到显著提高,减少术后并发症的发生。     

复方苦参注射液联合顺铂胸腔内注射治疗恶性血液病并发胸腔积液24例

目的:观察复方苦参注射液(岩舒)联合顺铂胸腔内注射治疗恶性血液病并发胸腔积液的临床疗效。方法:将46例恶性血液病并发胸腔积液患者随机分为治疗组(岩舒联合顺铂胸腔内注射治疗:顺铂20 mg·m-2+岩舒10 mL·m-2+地塞米松5 mg·m-2,每周1次,3～6次,n=24)。与对照组(顺铂胸腔内注射:顺铂20 mg·m-2+地塞米松5 mg·m-2,每周1次,3～6次,n=22)。比较两组胸腔积液的治疗效果和不良反应。结果:治疗组与对照组有效率分别为75.00%和63.64%,无显著差异;治疗组不良反应明显少于对照组(P<0.01)。结论:岩舒联合顺铂胸腔内注射治疗恶性血液病并发胸腔积液安全有效,且不良反应少。     

热疗联合胸腔内注射药物治疗恶性胸腔积液临床研究

目的:观察热疗加胸腔内注射顺铂治疗恶性胸腔积液的疗效和不良反应。方法:确诊为肿瘤所致的恶性胸腔积液的患者56例,随机分为两组。采用胸腔穿刺或胸腔闭式引流尽可能排尽胸水后,A组(28例)患者给予胸腔内注射顺铂60 mg,然后进行患侧胸腔深部热疗;B组(28例)患者只给予胸腔内注射顺铂60 mg。结果:两组总有效(胸水得到控制)率(A组85.71%,B组60.71%)比较差异有显著性(P<0.05),A组与B组生活质量好转率分别为75%和46.43%(P<0.05)。结论:热疗与DDP联合应用治疗恶性胸水有较好疗效,毒副反应小,可以改善患者生活质量,是安全有效的方法。     

Pharmacokinetics of etoposide after intrathoracic instillation to lung cancer patients with pleural effusion.

OBJECTIVE: To examine etoposide (VP16) levels in serum and pleural effusion after intravenous infusion or intrathoracic instillation to lung cancer patients. METHODS: Four patients were administered VP16 by intrathoracic instillation and three patients were administered it intravenously. Serum, urine, and pleural effusion were collected and VP16 levels in the biological fluids were determined by HPLC. Pharmacokinetic parameters were calculated. RESULTS: VP16 distributed rapidly into pleural effusion after intravenous infusion. In two of three patients, VP16 levels in pleural effusion were maintained at constant levels more than 24 hours in spite of the decline in serum VP16 levels. After intrathoracic instillation, VP16 in pleural effusion reached high levels and eliminated slowly. Serum levels of VP16 were relatively low compared with those in pleural effusion. CONCLUSION: It was demonstrated that intrathoracic instillation of VP16 might be useful for managing malignant pleural effusion and reducing systemic side-effects by cutting down the dose.     

复方苦参注射液联合顺铂胸腔灌注治疗恶性胸水的疗效观察

目的:为提高患者激活自身免疫细胞抗肿瘤活性,且杀灭胸水癌细胞的作用,达到减少恶性胸水及减轻患者痛苦的目的。方法:确诊为恶性胸水的患者共66例,随机分成两组,即复方苦参注射液、顺铂联合用药组与顺铂组,每组33例。两组患者在胸腔穿刺抽液后,分别注入不同药物处理,比较两种处理方法对消胸水灌注药物次数有无差别。结果:两组患者消胸水用药灌注次数及不良反应有差别(P<0.05)。复方苦参注射液、顺铂联合用药灌注组优于单纯顺铂灌注组。结论:复方苦参注射液、顺铂联合用药对激活免疫细胞抗肿瘤活性、杀灭癌细胞,促进胸膜粘连,既达到减少恶性胸水,又有提高患者抗病能力的作用。     

鸦胆子油乳联合顺铂治疗恶性胸腔积液临床观察

目的观察鸦胆子油乳联合顺铂胸腔内注射治疗恶性胸腔积液的疗效及不良反应。方法64例恶性胸腔积液患者,按数字表法随机分为治疗组和对照组各32例,经胸腔穿刺中心静脉导管置管引流胸腔积液,再向胸腔内注入药物;治疗组用鸦胆子油乳60—80ml／次,每周1次;顺铂60mg／m^2,用0．9％氯化钠注射液60ml稀释,每周1次;对照组单用顺铂60mg／m^2,每周1次;连续治疗4周观察疗效。结果两组有效率比较：治疗组为81．3％,对照组56．3％,两组差异有统计学意义（X^2=4．65,P〈0．05）;不良反应：两组差异无统计学意义（P〉0．05）。结论鸦胆子油乳联合顺铂胸腔内注射治疗恶性胸腔积液疗效确切,不良反应小,值得临床推广。     

腔内灌注化疗和热疗治疗癌性胸腹腔积液的疗效观察

目的 探讨腔内灌注化疗联合全身热疗在治疗癌性胸腹腔积液中的疗效.方法 将临床确诊的63例恶性胸腹腔积液患者随机分成3组,治疗组(21例)于排胸腹腔积液后腔内灌注顺铂(cis-diamminedichloroplatinum,DDP),30 min后即行红外线全身热疗,恒温期温度41.5～42℃,维持60 min以上;对照1组(21例)除不做全身热疗外,其余治疗同治疗组;对照2组(21例)除不做腔内灌注化疗外,其余治疗同治疗组.结果 3组患者经治疗后总有效率为43.6％,其中观察组有效率(76.2％)显著高于对照1组(33.3％)(P＜0.01)及对照2组(19.05％) (P＜0.001).结论 腔内化疗联合全身热疗治疗晚期肿瘤恶性胸腹腔积液较常规单纯腔内灌注化疗或单纯全身热疗效果好,能在一定程度上改善患者生活质量,有临床应用价值.     

卡铂、复方苦参注射液序贯胸腔灌注联合静脉化疗治疗恶性胸腔积液的疗效观察

目的:观察卡铂、复方苦参注射液序贯胸腔灌注联合静脉化疗治疗恶性胸腔积液的疗效和不良反应。方法:72例恶性胸腔积液患者随机均分为2组。胸腔置管充分引流后,试验组给予卡铂400mg,d1;复方苦参注射液30mL,d4、d7,胸腔注射。对照组仅给予卡铂400mg,d1,胸腔注射。全部患者在卡铂胸腔灌注前给予相应单药标准剂量静脉化疗,化疗同时予以常规对症、支持治疗。3周为1个治疗周期,治疗1个周期胸腔积液未达完全缓解(CR)者,可重复1个治疗周期(最多用药2个周期)。治疗结束后观察疗效和不良反应。结果:试验组控制胸腔积液有效率为91.7%,显著高于对照组(66.7%),差异有统计学意义(P=0.009);试验组胸腔积液CR率(75.0%)也显著高于对照组(47.2%),差异有统计学意义(P=0.016)。2组患者不良反应可耐受,发生率差异无统计学意义(P>0.05)。结论:从疗效和不良反应两方面衡量,卡铂、复方苦参注射液序贯胸腔灌注联合静脉化疗是治疗恶性胸腔积液的较好选择。     

复方苦参(岩舒)注射液联合顺铂治疗恶性胸腔积液的临床研究

目的:探讨复方苦参(岩舒)注射液联合顺铂治疗恶性胸腔积液的疗效。方法:将本院2002年12月—2008年12月168例恶性胸腔积液住院患者随机分为2组,均采用中心静脉导管胸腔留置持续负压吸引,放净胸水后化疗。试验组84例:顺铂40～60 mg+苦参60 mL胸腔灌注,5～7 d给予1次;对照组84例:顺铂40～60 mg胸腔灌注,5～7 d给予1次。结果:顺铂+苦参2药联合较单用顺铂疗效明显提高,不良反应轻(粒细胞减少发生率低),治疗组生活质量(KPS)评分试验组优于对照组,中位生存期和无疾病进展期较对照组延长。结论:岩舒注射液联合顺铂治疗恶性胸腔积液较单药顺铂治疗能提高恶性胸腔积液的控制率、提高生活质量、延长生存期;岩舒注射液联合化疗有保护骨髓功能的作用。     

微创置管胸腔内灌注顺铂联合全身化疗治疗肺癌患者胸腔积液的临床观察

目的 观察微创置管胸腔内灌注顺铂联合全身化疗治疗肺癌患者胸腔积液的疗效及不良反应.方法 选取60例肺癌伴胸腔积液患者,应用微创置管胸腔内闭式引流,局部灌注顺铂,并同时全身化疗,非小细胞肺癌用吉西他滨联合顺铂(GP方案)化疗,小细胞肺癌以依托泊苷联合顺铂(EP方案)化疗.结果 60例患者中胸腔积液完全缓解41例,部分缓解13例,稳定4例,进展2例,完全缓解率为68.3％(41/60),总有效率为90.0％(54/60).治疗后患者半年生存率为95.0％ (57/60),1年生存率为80.0％(48/60).局部联合全身化疗的不良反应主要是骨髓抑制和胃肠道反应.结论 微创置管胸腔内灌注顺铂联合全身化疗治疗肺癌患者胸腔积液疗效明显,不良反应均可耐受.     

Pharmacokinetics of paclitaxel and cisplatin in a hemodialysis patient with recurrent ovarian cancer

This is the first report that the combination of paclitaxel and cisplatin is feasible in a patient with recurrent ovarian cancer undergoing hemodialysis. Paclitaxel at a dose of 150 mg/m(2) was administered as a 3-h continuous i.v. infusion. Thirty minutes after paclitaxel administration, cisplatin was administered at a dose of 30 mg/m(2) for 30 min. Hemodialysis was started 30 min after completion of the cisplatin infusion and performed for 5 h. The maximum plasma concentrations of paclitaxel, total platinum and free platinum were 3.26, 2.44 and 1.84 microg/ml, respectively. The AUC of paclitaxel and free platinum were 15.3 and 1.76 microg x h/ml, respectively. The pelvic tumor size was reduced by 42% on MRI after the second course of this therapy. Grade IV neutropenia and grade III thrombopenia were observed. We conclude that paclitaxel and cisplatin combination chemotherapy is efficacious and feasible for an ovarian cancer patient under hemodialysis.     

微管胸腔闭式引流术灌注力尔凡和顺铂联合热疗治疗恶性胸腔积液的疗效观察

目的观察微管胸腔闭式引流术灌注腔内注入力尔凡及顺铂及热疗治疗恶性胸腔积液的疗效、生活质量和毒副反应。方法确诊为恶性胸腔积液的患者56例，随机分为两组，采用微管胸腔闭式引流术尽可能引流干净胸腔积液后，治疗组于腔内注入力尔凡90mg加DDP60～80mg，然后进行患侧胸腔的热疗。对照组只予DDP60～80mg腔内注入。结果治疗组控制恶性胸水的总有效率为86．2％，对照组为66．7％，P〈0．05；治疗组与对照组生活质量好转率分别为72.4％和40．7％．P〈0．05。结论采用微管胸腔闭式引流术热疗联合力尔凡及顺铂治疗恶性胸腔积液，疗效确切，并能明显提高患者生存质量，毒副反应能耐受。     

时间分辨荧光分析法测定抗原培养滤液蛋白10对结核性胸腔积液诊断的临床研究

目的 探讨时间分辨荧光免疫分析法(TRFIA)测定抗原培养滤液蛋白10(CFP10)对于早期诊断结核性胸腔积液的临床价值.方法 选择106例结核性胸腔积液病例与40例非结核性胸腔积液病例的胸腔积液标本.建立TRFIA法检测胸腔积液中CFP10抗原,并与酶联免疫吸附法(ELISA)的检测结果比较.结果 TRFIA法对CFP10抗原的平均回收率为96.87％,标准曲线相关系数r2=0.998,平均批内变异系数(CV)与批间CV分别为2.98％及4.20％,TRFIA法检测观察组CFP10的Log浓度为(1.924±0.57) μg·L-1,对照组为(0.108±0.03) μg·L-1,两组比较差异有统计学意义(t=24.72,P＜0.01).观察组ROC曲线的AUC=0.923.取临界值为11.86μg·L-1时,灵敏度与特异度分别为95.28％与92.50％,均高于ELISA法.结论 TRFIA法测定结核性胸腔积液中CFP10蛋白具有很高的灵敏度与特异度,有利于早期诊断结核性胸腔积液.     

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。