进口与国产紫杉醇治疗卵巢恶性肿瘤的疗效和药物经济学评价

目的比较进口与国产紫杉醇治疗卵巢恶性上皮性肿瘤(EOC)的疗效和经济学效果。方法 72例EOC患者按手术残余灶大小及使用进口紫杉醇和国产紫杉醇分为TS组(进口紫杉醇且术后残余病灶直径≤1 cm)和PS组(国产紫杉醇且术后残余病灶直径≤1 em)、TU组(进口紫杉醇且术后残余病灶直径>1cm)和PU组(国产紫杉醇且术后残余病灶直径>1 cm)。4个化疗周期结束后评价疗效和不良反应,并用最小成本分析法进行药物经济学研究。结果 TS组vs PS组和TU组vs PU组第1～4疗程治疗效果与不良反应差异均无统计学意义(P>0.05),进口紫杉醇-卡铂与国产紫杉醇-卡铂两种治疗方案成本分别为44073.89元和12 689.89元。结论进口与国产紫杉醇对EOC患者的近期疗效相似,国产紫杉醇-卡铂治疗EOC患者在药物经济学上优于进口紫杉醇-卡铂方案。     

紫杉醇在卵巢癌化疗病人中的非线性药物动力学(英文)

目的:探讨紫杉醇在卵巢癌病人体内的药物动力学特点。方法:15名紫杉醇化疗病人3小时内输注剂量分别为135mg/m~2,175mg/m~2和235mg/m~2。输注过程中及输注后24小时采集病人血样。由非房室和房室模型评价药物动力学参数。结果:化疗病人符合二室模型,三组的T_((1/2)β)分别为(5.18±3.49,6.26±2.21和6.99±1.45)h,AUC(14.71±0.76,39.09±13.10和66.52±12.23)mg·h·L~(-1),Cl(14.29±0.74,7.52±2.15和6.25±1.93)L·h~(-1)。结论:紫杉醇具有非线性药物动力学特征,病人的代谢存在个体差异。     

The reversal of multidrug resistance in ovarian carcinoma cells by co-application of tariquidar and paclitaxel in transferrin-targeted polymeric micelles

In this study, a transferrin (Tf)-modified polyethylene glycol-phosphatidyl ethanolamine (PEG-PE)-based micellar delivery system containing paclitaxel (PTX) and tariquidar (TRQ), a potent third generation P-gp inhibitor, was prepared. The nanoformulation was evaluated by targeting efficiency, cellular association, cellular internalization pathway and cytotoxicity for reversal of PTX resistance on two multidrug resistant (MDR) ovarian carcinoma cell lines, SKOV-3TR and A2780-Adr. PTX and TRQ are both hydrophobic compounds. They were successfully encapsulated into the micellar structure containing vitamin E as the encapsulation enhancer. The Tf-targeted micelles were internalized mainly via clathrin-dependent endocytosis by both cell lines. For SKOV-3TR, additional mechanisms including caveolin-dependent endocytosis and macropinocytosis were found to play a significant role. The PTX cytotoxicity against the SKOV-3TR and A2780-Adr MDR cells was increased significantly in the presence of micellar encapsulation. However, unlike the A2780-Adr cell line, the Tf-targeting effect was significant on SKOV-3TR cells when co-administrated with TRQ. Penetration of the Tf-targeted micelles in a cancer cell spheroid culture was also investigated.     

术前介入治疗对1b2期宫颈癌近期疗效的观察

目的 研究巨块型宫颈癌Ib2期术前介入化疗加血管栓塞的近期疗效.方法 对我院收治的Ib2期宫颈癌患者56例,按术前治疗方法不同分术前介入化疗加血管栓塞联合后装放疗组(A组)及术前后装放疗组(B组),治疗后2.3周两组患者均行广泛全子宫加盆腔淋巴结清扫术.结果 介化联合后装组的症状缓解率为100%,近期有效率达100%,单纯后装组的症状缓解率为100%,近期有效率为76.5%.两组的有效率和症状缓解率具有明显的差异(P＜0.05).结论 对于Ib2期宫颈癌患者,采用术前介入化疗联合放疗的方法可明显改善症状,提高宫颈癌的疗效.     

Escalating doses of paclitaxel and epirubicin in combination with cisplatin in advanced ovarian epithelial carcinoma: a phase I-II study

Our objective was to identify a new active three-drug combination regimen consisting of paclitaxel (PTX), epirubicin (EPI) and cisplatin as first-line line chemotherapy for advanced ovarian carcinoma. A phase I study was carried out to evaluate the dose-limiting toxicity (DLT) and the maximally tolerated dose (MTD) of PXT and EPI in combination with a fixed dose of cisplatin every 4 weeks. Side-effects were recorded according to the NCI Common Toxicity Criteria. Patients were treated in cohorts of three with fixed-dose cisplatin 80 mg/m2 and EPI 80-->100 mg/m2 and PXT 100-->160 mg/m2 until DLT was reached. Once MTD was identified, a single-step phase II study was therefore carried out to test the clinical activity and panel of toxicity of such regimen. Objective responses were recorded according to the WHO criteria. Time to progression and overall survival (OS) were secondary endpoints. The DLT was myelosuppression and, in more detail, febrile neutropenia, which occurred at the fifth dose level (PTX 140 mg/m2, EPI 100 mg/m2 and cisplatin 80 mg/m2) in two out of three patients. Other side-effects were grade 3 mucositis in two out of three patients and grade 3 anemia in one case. The combination of cisplatin 80 mg/m2 plus EPI 80 mg/m2 and PCT 140 mg/m2 every 4 weeks was considered as the MTD. In the phase II study a complete response was observed in six patients (33%) and a partial response in nine cases (50%) for an overall response rate of 83% [95% confidence limits (CL) 59-96%]. Median time to progression of patients with measurable disease was 16.4 months. Median OS was not reached after a follow-up of 42 months. This study demonstrated that PTX and EPI can be safely administered in combination with cisplatin to fit patients with advanced epithelial ovarian carcinoma. The three-drug regimen of cisplatin 80 mg/m2, EPI 80 mg/m2 and PTX 140 mg/m2 every 4 weeks is very active, at least in terms of objective response rate. This level of activity overlaps with the 95% CL of the activity of cisplatin alone; however, it does encourage future trials of the combination.     

Inhibition of HER-2 by three independent targeting strategies increases paclitaxel resistance of SKOV-3 ovarian carcinoma cells

Current treatment options for ovarian cancer, which is one of the most widespread gynecological malignancies, are limited, mainly because patients with advanced-stage disease often develop resistance to chemotherapeutics. In breast cancer cells, several studies suggest that overexpression of the human epidermal growth factor receptor-2 (HER-2) leads to increased resistance against certain, but not all cytotoxic drugs. In ovarian carcinoma, conflicting data on the correlation of HER-2 expression and tumor cell sensitivity exist. In this paper, we explore the role of HER-2 expression and signaling levels pertaining to paclitaxel (Taxol) chemoresistance by applying three different and independent strategies in SKOV-3 ovarian carcinoma cells. Firstly, we show that treatment with the HER-2 inhibitory antibody trastuzumab (Herceptin), which is well established in tumor therapy, results in markedly increased, rather than decreased, cellular paclitaxel resistance. Next, we present two newly developed low molecular weight inhibitors of HER-2 tyrosine kinase activity, D-69491 and D-70166. With both drugs, the decrease in cellular paclitaxel sensitivity upon HER-2 inhibition is confirmed. Finally, for more detailed analysis we stably downregulate HER-2 expression by ribozyme-targeting. Using clonal ribozyme-transfected SKOV-3 cells with different residual HER-2 levels, we establish a HER-2 gene dose effect of paclitaxel cytotoxicity. We show that this effect is due to differential induction of apoptosis and differential cell cycle inhibition by paclitaxel. Finally, paclitaxel- or HER-2-mediated alterations in the phosphorylation of MAP kinases p42/44, Stress-activated protein kinase/Jun-terminal kinase (SAPK/JNK), and p38, and effects on the activation of caspase-3, caspase-7, and bcl-2 are discussed. We conclude that paclitaxel cytotoxicity in SKOV-3 cells is HER-2 dose-dependent and identify cell proliferation as one underlying cellular event of this effect.S. Abuharbeid and J. Apel contributed equally to the work     

A rare case of advanced ovarian carcinoma who developed difficulty walking 25 days after treatment with weekly paclitaxel

Although taxol has shown significant activity in advanced ovarian cancer, peripheral neuropathy is likely to become the major dose-limiting toxicity. We describe a case of advanced ovarian carcinoma who developed difficulty walking because of marked pain in the lower extremities and loss of proprioception 25 days after treatment with weekly taxol (80 mg/m(2)x3).     

CyclinD1在卵巢上皮性及生殖细胞肿瘤中的表达

目的 :探讨癌基因 CCND1的蛋白表达产物 Cyclin D1在卵巢上皮性肿瘤、生殖细胞肿瘤中的表达及临床意义。方法 :采用免疫组化 PAP方法研究 10 0例卵巢上皮性肿瘤组织、生殖细胞肿瘤组织中 Cyclin D1蛋白的表达情况。结果 :Cyclin D1蛋白在卵巢良性、交界性、恶性肿瘤中的表达具有显著性差异 (P<0 .0 5 )。Cyclin D1蛋白的表达率随着临床分期的增高呈现出具有统计学意义的增高。在有淋巴结转移、腹水细胞学检查癌细胞阳性、远处脏器转移的患者中 Cyclin D1蛋白阳性表达率 ,与无转移者比较差异具有显著性意义 (P<0 .0 5 )。结论 :Cyclin D1蛋白的过度表达 ,在卵巢肿瘤的发生、发展过程中起作用 ,与卵巢癌的临床分期、淋巴结转移、远处脏器转移有关。通过检测卵巢肿瘤组织中 Cyclin D1蛋白的表达可用来预测肿瘤患者的预后     

Chronic administration of single weekly paclitaxel in heavily pretreated ovarian cancer patients

Ovarian cancer patients with paclitaxel-resistance have been reported to respond to a weekly schedule of the same drug. In this report, two cases with long progression free interval by weekly paclitaxel (T) are presented. Case 1. A 41-year-old Japanese woman, gravida 2, para 0, was referred to our hospital in September 16, 1998, because of abdominal mass accompanying large amount of ascites with elevated CA125 (8400 U/ml) and CA19-9 (770 U/ml). Exploratory laparotomy (tumor biopsy plus partial omentectomy) was performed September 21, 1998. After the surgery, the tumor was diagnosed as serous cystadenocarcinoma of the ovary (stage IV) and 6 cycles of treatment consisting of cyclophosphamide, adriamycin and cisplatin (CAP) were performed. The CA 125 level (8400 U/ml) rapidly declined to 150 U/ml by this CAP therapy. After second cytoreductive surgery (SRS) (total hysterectomy and bilateral salpingo-oophorectomy), residual tumor was less than 2 cm. Although 7 cycles of CAP was added, ascites and elevation of CA 125 (5100 U/ml) were observed. Therefore, treatment with single weekly T was performed and CA 125 levels remained between 70-90 U/ml during 13 cycles of this therapy (progression free interval; more than 1 year). Thereafter, she is alive with disease and followed-up. Case 2. A 48-year-old Japanese woman, gravida 3, para 2, was referred to our hospital in July 22, 1998, because of abdominal swelling and pain. Computing tomography (CT) and magnetic resonance imaging (MRI) revealed large amount of ascite and pelvic mass (9 x 7 x 7 cm), and low density area (3 x 3 cm) suggesting metastasis in right lobe of liver. Serum CA 125 level elevated to 5100 U/ml. Bilateral salpingo-oophorectomy and infracolic omentectomy were performed on August 5, 1998. The tumor was diagnosed as endometrioid adenocarcinoma of the ovary, stage IV and chemotherapy with CAP was initiated on September 5, 1998. After 6 cycles of CAP, SRS was performed. After SRS, 3 cycles of CAP were added and changed to weekly T because of damage of renal function. The CA 125 level returned within normal range during weekly T. Total 13 cycles of weekly T were performed and progression free interval was about 18 months. Thereafter, she received treatments with gamma knife and CAP for brain metastasis. She is alive without disease and followed-up. Side effects by weekly T were mild and tolerable despite of long term treatment. In addition, weekly T can be safely used in outpatient setting and even in patients with poor performance status (PS), and warrant long time to progression.     

紫杉醇对鼻咽癌放疗增敏的临床研究

目的 评价鼻咽癌患者在放疗过程中用紫杉醇增敏的治疗效果。方法 共治疗鼻咽癌患者46例，随机分成两组．23例单纯放疗；23例放疗同时给予国产紫杉醇增敏，90mg，静脉滴注，1次／w .结果 单纯放疗达到部分缓解的为12例，给予紫杉醇放疗增敏的23例患者中，达到部分缓解的为21例。结论 紫杉醇增敏优于单纯放疗。     

The prognostic role of FIGO stage in patients with vulvar cancer: a systematic review and meta-analysis

Objective: To perform a meta-analysis examining the survival of patients with vulvar cancer based on the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system. Methods: Medline, PubMed, and Cochrane databases were searched until 20 March 2015 for prospective or retrospective studies using the terms vulvar cancer, prognostic/prognosis, survival, recurrence, lymph nodes (LNs), inguinal lymphadenectomy/excision, and staging. The primary outcome was 5 year overall survival (OS), and secondary outcomes were 5 year disease-free survival (DFS) and progression-free survival (PFS). Results: Fourteen retrospective studies were included. The 5 year OS rate decreased with increasing 2009 FIGO stage and number of LN metastasis. FIGO stage I, II, III, and IV patients had 5 year OS rates of 84.0%, 74.6%, 47.8%, and 9.4%, respectively. Pooled estimates showed that the 5 year OS was 84.5% for patients without LN metastasis, and for patients with ≥3 LN metastases the 5 year OS rate was 30.1%. Similarly, the overall 5 year DFS and PFS decreased with the increasing number of LN metastases. The 5 year DFS rate was 87.2% for patients with no LN metastasis and for patients with ≥3 LN metastases was 35.4%. The 5 year PFS rate was 86.6% for patients with no LN metastasis and for patients with ≥3 LN metastases was 27.6%. Limitations: All studies were retrospective studies. DFS and PFS rates in patients with different 2009 FIGO stages and with different mean tumor sizes were not examined due to a limited number of reports. Conclusions: More advanced 2009 FIGO stage and greater number of LN metastases are associated with worse outcomes in patients with vulvar cancer.     

紫杉醇脂质体与传统紫杉醇治疗卵巢癌的疗效分析

目的：比较紫杉醇脂质体（力朴素）和传统紫杉醇治疗卵巢癌的疗效及不良反应。方法：查阅2009年1月～2010年5月在本院治疗的卵巢癌患者140例,根据用药情况分为试验组和对照组,试验组（70例）应用力朴素每次剂量为135～175mg/m2,对照组（70例）应用传统用紫杉醇,每次剂量为135～175mg/m2,两组均联合卡铂治疗,每3周重复1次为1个周期,其中力朴素治疗化疗2个疗程的患者有41例,化疗6个疗程的有29例,术后化疗的有62例,直接行化学治疗的有8例。传统紫杉醇化疗2个疗程的患者有46例,6个疗程的有24例,术后化疗的有57例,直接化疗的有13例。结果：与术后接受6个疗程化疗的患者用药比较,应用紫杉醇脂质体（试验组）明显优于紫杉醇（对照组）,其溶媒所产生的变态反应,紫杉醇脂质体（力朴素）明显低于紫杉醇,其余不良反应两组患者相仿。结论：紫杉醇脂质体联合铂类治疗卵巢癌效果良好,两种紫杉醇疗效相当,但术后接受6个疗程的患者用药比较,紫杉醇脂质体（试验组）疗效明显优于紫杉醇（对照组）。其溶媒所产生的变态反应,紫杉醇脂质体（力朴素）明显低于紫杉醇,其余不良反应两组相仿。     

Primary systemic therapy with intermittent weekly paclitaxel plus gemcitabine in patients with stage II and III breast cancer: a phase II trial

The purpose of this study was to evaluate pathologic complete response (pCR) rates and adverse events with primary systemic therapy (PST) of intermittent weekly paclitaxel and gemcitabine in patients with stage II and III breast cancer. Node-positive patients with stage II and III breast cancer received paclitaxel 80 mg/m² followed by gemcitabine 1,200 mg/m² on day 1 and day 8, every 3 weeks for four cycles. Postoperatively, four cycles of doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks were given. Of 44 enrolled patients, 73% had stage III breast cancer with 68% hormone-receptor positive and 41% HER2 positive tumors. Eight patients achieved pCR in primary tumors (18%), 11 in axillary nodes (25%), and five in both tumor and axillary nodes (11%). Breast conservation was possible in 28 patients (64%). Grade III/IV toxicities were neutropenia (57%), leukopenia (14%), febrile neutropenia (2%), and headache (2%). In conclusion, PST with intermittent weekly paclitaxel and gemcitabine in patients with stage II/III breast cancer is both well tolerated and effective, showing 18% pCR rate in the breast.     

探讨紫杉醇联合顺铂腹腔和静脉双途径治疗晚期卵巢癌的临床疗效

目的 总结紫杉醇联合顺铂腹腔和静脉双途径治疗晚期卵巢癌的临床疗效.方法 将2014年1至12月在本院入院治疗的72例晚期卵巢癌患者纳入本组研究中,按照给药方式的不同将72例患者分为双途径组(n=36)与常规组(n=36),常规组采用常规静脉给药法,双途径组使用紫杉醇联合顺铂腹腔和静脉双途径疗法,统计两组疗效及3年总生存率.结果 在肿瘤变化、腹水控制、CA125指标变化与治疗有效率上,双途径组疗效更为理想,上述数据组间比较差异均有统计学意义(均P＜ 0.05);针对患者进行随访,随访截止时间为2016年12月,观察患者的3年生存率,双途径组的3年生存率为50.0％,常规组的3年生存率为27.8％,经Log-rank检验对比,两组患者的3年总生存率差异有统计学意义(Log-rank=4.278,P=0.039).结论 对于晚期卵巢癌患者,紫杉醇联合顺铂腹腔和静脉双途径疗法行之有效,可以有效控制患者腹水、缩小肿瘤直径,临床疗效理想,并能有效地改善患者的预后.     

不同剂型紫杉醇联合卡铂对复发性卵巢癌患者的成本-效果分析

目的 探讨不同剂型紫杉醇联合卡铂对复发性卵巢癌患者的成本-效果。方法 选取滁州市第一人民医院2016年5月—2018年5月收治的60例复发性卵巢癌患者为研究对象，随机将其分为对照组与观察组，每组30例。对照组患者第1日给予175 mg/m²的传统紫杉醇注射液，加入到5%葡萄糖注射液500 mL中，静脉滴注3 h，给药前给予地塞米松预处理。次日采用5 AUC卡铂注射液，加入5%葡萄糖注射液500 mL，静脉滴注2 h。观察组患者给予175 mg/m²注射用紫杉醇脂质体，加入5%葡萄糖注射液500 mL，静脉滴注3 h；5 AUC卡铂注射液加入到5%葡萄糖注射液500 mL中，静脉滴注2 h。21 d为1个周期，两组共治疗6个周期。结果 治疗后，观察组临床总有效率为66.67%，与对照组的60.00%相比，差异不具有统计学意义。治疗期间，观察组患者的毒副反应率为20.00%，显著低于对照组46.67%，两组比较差异具有统计学意义（P<0.05）。观察组的化疗药物使用费用高于对照组，毒副反应治疗药物低于对照组，两组比较差异有统计学意义（P<0.05）。观察组的增量成本-效果比（△C/△E）为7 234.65，即增加1个效果单位，观察组需多花7 234.65元。结论 复发性卵巢癌患者采用传统紫杉醇联合卡铂治疗具有较高的疗效及经济性，值得临床推广应用。     

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.     

Overcoming platinum resistance in ovarian carcinoma

Importance of the field: Ovarian cancer remains a deadly malignancy because most patients develop recurrent disease that is resistant to chemotherapy, including platinum. Because response rates for current treatment regimens are relatively similar and unfortunately low, no standard chemotherapy for platinum-resistant ovarian cancer exists.

Areas covered in this review: A systematic literature review of clinical studies published between January 2005 and March 2010 was conducted using search engines, PubMed and MEDLINE with the entry keywords ‘ovarian cancer’ and ‘platinum resistance’. This search revealed 40 clinical trials (1793 patients).

What the reader will gain: Gemcitabine was the most common drug used in clinical trials reporting higher response rates, ≥ +1 SD of overall response rate (5 out of 8). Gemcitabine-based combination therapy showed an average response rate of 27.2% (95% CI, 22.4 – 32.0). Combination of gemcitabine and pegylated liposomal doxorubicin (PLD) was the most common regimen (n = 3) and was associated with possible additive effects in platinum-resistant ovarian cancer patients: response rate, gemcitabine alone 6.1%, PLD alone 19.8%, and gemcitabine with PLD 28.7% (95% CI, 20.4 – 37.0), respectively.

Take home message: Analysis of recent clinical trials showed that gemcitabine-based combination chemotherapy was associated with the highest antitumor effects in platinum-resistant ovarian cancer patients during the study period.     

子宫内膜癌临床及 MRI分期与手术病理分期的对比

目的：对比子宫内膜癌患者临床分期、MRI分期以及手术病理分期三者之间的差别,并分析各自的临床价值。方法回顾性分析该院2012年2月－2014年2月收治的85例子宫内膜癌患者的临床资料,并对其临床分期、MRI分期以及手术病理分期进行对比。结果临床分期Ⅰ期66例,51例与MRI分期相符,43例与手术病理分期相符;临床分期Ⅱ期19例,9例与MRI分期相符,7例与手术病理分期相符;MRI分期Ⅰ期41例与手术病理分期相符,Ⅱ期15例相符,Ⅲ期11例相符;临床分期与MRI分期总符合率70．59％,与手术病理分期总符合率58．82％,MRI分期与手术病理分期总符合率78．82％。结论手术前进行的临床分期准确度较低,准确度随期别的提高而降低;MRI分期可以多方位且清晰地显示患者体内肿瘤病灶部位和病变范围;手术病理分期最能显示肿瘤病变部位范围以及淋巴结转移情况,具有较大的判断价值。