拓扑替康作为二线药物治疗上皮性卵巢癌的临床研究

目的 :探讨拓扑替康作为二线药物治疗卵巢上皮癌的疗效及安全性。方法 :经病理证实的卵巢上皮癌 4 0例 ,均可评价疗效和毒副作用。静脉滴注拓扑替康 1.2mg (m2 ·d)30min ,每日 1次 ,连用 5d ,2 1d为 1周期 ,2周期评价疗效。结果 :完全缓解率为 5 .0 % ,部分缓解率为 17.5 % ,总有效率为 2 2 .5 %。主要毒副作用为骨髓抑制 ,非血液学毒性轻微 ,均可耐受。结论 :拓扑替康是治疗卵巢上皮癌的有效的二线药物。     

初治卵巢上皮癌组织中P-gp的表达及其临床意义

目的:探讨初治卵巢上皮癌组织中P-gp的表达及其临床意义。方法:免疫组化法检测90例初治卵巢上皮癌组织中P-gp的表达,并分析其与卵巢上皮癌临床病理特征、化疗敏感性、复发、预后的关系。结果:90例卵巢上皮癌P-gp阳性率为68.89%。P-gp表达与患者FIGO分期、复发有关,P-gp阳性率Ⅲ、Ⅳ期较Ⅰ、Ⅱ期(P=0.024)高,有复发组较无复发组(P=0.000)高。P-gp表达与年龄、肿瘤家族史、血型、术前CA125、病理类型、病理分级无关(P>0.05)。P-gp表达与铂类化疗耐药呈正相关(r=0.215,P=0.042)。P-gp阳性组复发率高于阴性组(58.06%vs14.29%,P=0.000)。单因素分析显示FIGO分期晚、低分化、P-gp表达、有复发的患者预后差(P<0.05)。预后的COX多因素分析显示:仅FIGO分期(RR=1.649,P=0.047)是影响卵巢上皮癌患者预后的独立因子。结论:初治卵巢上皮癌中存在P-gp的阳性表达,P-gp表达与FIGO分期、化疗耐药、复发有关。     

复发性耐药性卵巢恶性生殖细胞肿瘤的治疗

恶性生殖细胞肿瘤治疗关键是规范化,包括手术切除肿瘤、手术病理分期、术后规范化疗,强调及时、足量、正规,可争取90%以上甚至100%的持续缓解率。初次化疗不规范,病情可能持续不缓解或复发。对于复发性恶性生殖细胞肿瘤,再次肿瘤细胞减灭术有减轻瘤负荷的作用,为术后的化疗奠定基础。复发性卵巢恶性生殖细胞肿瘤术后的二线化疗也至关重要。化疗药物应个体化,化疗的疗程数也强调个体化,有阳性肿瘤标志物的患者治疗应持续至肿瘤标志物降至正常后2个疗程。无阳性的肿瘤标志物的患者治疗应持续4~6个疗程。无性生殖细胞瘤和未成熟畸胎瘤对再次化疗或手术仍有效,预后好。卵黄囊瘤则效果很差。卵巢胚胎癌及原发绒癌很少见,治疗经验少。     

二探阳性的卵巢上皮癌病人腹腔顺铂与静脉泰素化疗

初次肿瘤细胞减灭术后,晚期卵巢癌的标准治疗为包括泰素、铂类的联合化疗。尽管上述治疗可达到完全缓解,大多数病人仍有持续性肿瘤或肿瘤复发。腹腔化疗一直被视为持续性肿瘤的二线治疗。为分析对铂类敏感且二探中发现有小块肿瘤(<1 cm)的卵巢上皮癌病人再行腹腔顺铂灌注化疗与静脉泰素联合化疗的结果,收集1995年6月～1998年6月在MSKCC初治为Ⅲ或Ⅳ期卵巢上皮癌病人,     

复发性上皮性卵巢癌二线化疗的回顾性分析

目的 探讨复发性上皮性卵巢癌二线化疗的疗效及可行性。方法 回顾性分析51例复发性卵巢上皮性恶性肿瘤，其中32例用顺铂 异环磷酰胺 足叶乙甙方案及顺铂 拓扑替康化疗。结果 二线化疗有效率62．5％；二线化疗后平均生存期13．54个月，明显高于未治疗组。但总生存期无差别。两种化疗方案(PIE化疗组和拓扑替康组)相比对生存期影响无明显差别。结论 顺铂、异环磷酰胺加足叶乙甙及顺铂 拓扑替康联合化疗治疗复发及难治性上皮性卵巢癌有一定疗效，可供临床选用。     

复发性卵巢癌的治疗选择——手术还是化疗

复发性卵巢癌的治疗是妇科肿瘤中棘手的问题,一般包括再次手术和挽救化疗.对铂类敏感的复发性卵巢癌,可以在二次肿瘤细胞减灭术的基础上,再使用铂类为基础的联合化疗方案.对铂类耐药的复发性卵巢癌,根据患者的具体情况,权衡手术和化疗的利弊,挽救化疗时宜选择其他二线化疗药物进行单药序贯化疗.对复发性卵巢癌手术,要严格选择、充分准备,尽可能完全切除复发癌灶,为挽救化疗创造有利条件.     

复发性卵巢癌的治疗选择——手术还是化疗

复发性卵巢癌的治疗是妇科肿瘤中棘手的问题，一般包括再次手术和挽救化疗。对铂类敏感的复发性卵巢癌。可以在二次肿瘤细胞减灭术的基础上，再使用铂类为基础的联合化疗方案。对铂类耐药的复发性卵巢癌，根据患者的具体睛况，权衡手术和化疗的利弊，挽救化疗时宜选择其他二线化疗药物进行单药序贯化疗。对复发性卵巢癌手术。要严格选择、充分准备，尽可能完全切除复发癌灶，为挽救化疔创造有利条件。     

监测外周血SCF对预测c-kit阳性上皮性卵巢癌化疗耐药的临床价值

目的:监测卵巢癌患者外周血中游离干细胞因子(SCF)的浓度变化和c-kit蛋白在卵巢癌组织中的表达,探讨外周血SCF值对早期预测c-kit(+)上皮性卵巢癌继发性化疗耐药的临床价值。方法:利用量子点双染免疫荧光(QDs)检测106例卵巢癌组织中c-kit和SCF蛋白表达,ELISA法检测46例上述卵巢癌患者化疗期间冰冻保存的外周血SCF值,分析铂类为主的化疗药物敏感型和耐药型卵巢癌患者外周血SCF值与组织ckit表达的差异。结果:继发性化疗耐药的上皮性卵巢癌组织中,c-kit(+)表达率远高于化疗敏感组(29.27%vs 10.8%,P0.05),c-kit(+)表达率随着FIGO分期的进展而升高(Ⅰ~Ⅱ期8.7%,Ⅲ~Ⅳ期25%,P0.05)。继发性化疗耐药组的外周血SCF值随铂类为主的化疗药物治疗而有升高的趋势,化疗敏感组的SCF值随之有下降的趋势;继发性化疗耐药组的外周血SCF均值高于化疗敏感组(P0.05)。卵巢癌c-kit(+)的外周血SCF值均值高于c-kit(-)组(P=0.018),外周血SCF值在卵巢癌c-kit(+)组随铂类为主的化疗耐药而升高。结论:卵巢上皮癌组织中c-kit蛋白阳性表达可能导致肿瘤对铂类化疗药物耐药;c-kit蛋白在肿瘤间质细胞内的阳性表达,预示卵巢上皮性癌化疗耐药微环境的形成和极差的临床结局。卵巢癌化疗期间,监测外周血SCF值升高可能是早期预测c-kit(+)卵巢癌继发性化疗耐药的标记物之一。     

经阴道穿刺配合药物治疗卵巢巧克力囊肿108例疗效观察

目的 :观察经阴道穿刺注入无水乙醇配合药物治疗卵巢巧克力囊肿的疗效。方法 :对 10 8例卵巢巧克力囊肿患者在阴道B超引导下行囊肿穿刺 ,注入无水乙醇之后随机分为 3组 :GnRHa组、内美通组、对照组。观察其缓解率、复发率、复发所需时间及妊娠率。结果 :缓解率GnRHa组 90 0 0 % ,内美通组 84 2 1% ,明显高于对照组 5 6 6 7%。复发率GnRHa组 12 5 % ,内美通组 2 1 0 5 % ,明显低于对照组 4 3 33%。妊娠率GnRHa组 2 7 5 % ,内美通组 2 3 6 8% ,明显高于对照组 6 6 7%。结论 :经阴道穿刺配合药物治疗卵巢巧克力囊肿缓解率、妊娠率较高 ,复发率低     

谷胱甘肽作为预测卵巢癌对二线化疗反应的指标

以铂类为基础的联合化疗是卵巢癌的标准化疗。其初治疗有效率为76%,但肿瘤复发后则疗效降至20%,为寻找一种可反映肿瘤对二线化疗有效与否的物质及其指标,通过检测肿瘤内谷胱甘肽-S-转移酶-π(GST-π)的表达或谷光甘肽(GSH)浓度,探讨其与患者对二线化疗反应性之间的关系。     

卵巢上皮性癌P-糖蛋白表达及其与化疗耐药性的关系

目的：了解多药耐药ＭＤＲ基因在卵巢癌中的表达及表达产物Ｐ－糖蛋白（Ｐ－ｇｐ）与化疗耐药性的关系。方法：用免疫组化法测定卵巢癌５４例手术切除肿瘤组织Ｐ－ｇｐ的表达情况，分析其与临床、病理及化疗效果的关系。结果：Ｐ－ｇｐ表达阳性者２４例，占４４．４％，Ｐ－ｇｐ表达与临床分期、病理分级、术后残余瘤大小无关。Ｐ－ｇｐ阳性与阴性者所接受的化疗无差异。术前用过与ＭＤＲ有关药物化疗者，Ｐ－ｇｐ阳性率为６９．２％，高于未化疗者（３６．６％）。Ｐ－ｇｐ阳性者化疗近期疗效差，化疗有效率为４７．１％，低于Ｐ－ｇｐ阴性者的８１．８％，但两组预后无差异。结论：测定Ｐ－ｇｐ表达有助于预测肿瘤的耐药性及指导化疗药物的选择。Ｐ－ｇｐ表达是化疗耐药原因之一。     

复发性卵巢上皮性癌再次手术的临床评价

目的　探讨复发性卵巢上皮性癌 (卵巢癌 )再次手术的指征及临床意义。方法　复发性卵巢癌再次手术的患者 5 5例 ,术前及术后均进行化学药物治疗 (化疗 )或放射治疗 (放疗 ) ,再次手术共 6 8例次。根据再次手术前不同病灶的性质分为 4组 ,即单个复发灶组、多个复发灶组、因肠梗阻手术组及姑息性手术组。并根据再次手术前对化疗的敏感程度分为 3组 ,即≤ 6个月复发组、>6个月复发组及肿瘤进展组。观察每组再次手术中进行满意的肿瘤细胞减灭术的例数、手术并发症的例数及手术治疗的有效率、生存时间、疾病缓解时间。结果　再次手术前通过检查认为是单个复发灶者 ,6 1%在再次手术中发现为多个复发灶 ;单个复发灶组中获得较满意的肿瘤细胞减灭术的为 6 7% ,术前认为是单个复发灶者而在再次手术中确诊为多个复发灶者中 ,获得较满意的肿瘤细胞减灭术的为6 4 % ;多个复发灶组获得满意的肿瘤细胞减灭术的为 4 3%。再次手术治疗的有效率 ,以单个复发灶组最高 ;手术后疾病缓解时间及生存时间 ,也以单个复发灶组最长 ;单个复发灶组手术并发症少于多个复发灶组。获得满意的肿瘤细胞减灭术 ,停止化疗 >6个月复发组为 73% ;≤ 6个月复发组为80 % ;肿瘤进展组为 5 0 %。结论　单个复发灶组、停止化疗 >6个月复发组再次手     

Result of individualized chemotherapy with a newly developed in vitro chemosensitivity testing in ovarian cancer

By means of a newly developed in vitro chemosensitivity test based on the morphological changes in the nucleus (nuclear damage assay) as previously described, we were able to screen currently available anticancer drugs within 24 hr with a 100% success rate. The nuclear damage assay was used to determine the chemosensitivity in 50 patients (66 assays) with ovarian cancer. The response rate for the 13 patients with measurable tumors, 8 of whom showed resistance to CAP (cyclophosphamide, adriamycin, and cisplatin) therapy, was 46 percent when they were given various combination chemotherapy protocols consisting of more than one active agent selected from group A and B agents by the nuclear damage assay. The newly developed in vitro chemosensitivity test proved to be useful when selecting a second line combination for patients with CAP-resistant ovarian cancer.     

Salvage chemotherapy for ovarian cancer recurrence: weekly cisplatin in combination with epirubicin or etoposide

From December 1986 to April 1990, 40 consecutive ovarian cancer patients who relapsed after response to cisplatin-based chemotherapy regimens were treated with seven courses of weekly cisplatin, in combination with epirubicin or etoposide. The overall response rate obtained with the intensive schedule was 60% and the complete response rate was 25%; median duration of response was 7 months and median survival time, 13.5 months. Responsive cases seem to have longer survival; a prognostic factor for response to salvage treatment and longer survival is the disease-free interval after the first-line chemotherapy. Weekly cisplatin as intensive treatment was very well tolerated and showed acceptable toxicity in both the combination protocols with epirubicin or etoposide.     

腹腔热灌注联合多西他赛、奥沙利铂静脉化疗治疗晚期卵巢癌疗效观察

目的:探讨肿瘤细胞减灭术(CRS)后腹腔热灌注联合多西他赛、奥沙利铂静脉化疗治疗晚期卵巢癌的临床疗效。方法:取2011年1月至2014年12月在河北医科大学第二医院就诊的晚期卵巢癌患者42例,其中观察组21例(CRS后+腹腔热灌注+多西他赛、奥沙利铂静脉化疗)、紫杉醇+卡铂组21例(CRS后+紫杉醇、卡铂静脉化疗)。比较两组的疗效、肿瘤控制、腹水控制、生活质量、治疗过程中的不良反应及并发症、无进展生存期(PFS)等。结果:观察组与对照组肿瘤控制差异无统计学意义(P0.05);腹水控制、生活质量、PFS均优于对照组,差异有统计学意义(P0.05)。不良反应及并发症无明显差异(P0.05)。结论:在临床上对于晚期卵巢癌患者采取CRS术后腹腔热灌注联合多西他赛、奥沙利铂静脉化疗,对于患者的疗效、肿瘤控制、腹水控制、生活质量、PFS有提高,且不明显增加不良反应及并发症。     

No rules without exception: long-term complete remission observed in a study using a LH-RH agonist in platinum-refractory ovarian cancer

OBJECTIVE: Second-line chemotherapy in platinum/paclitaxel-resistant ovarian cancer induces an objective response in <15% and third-line chemotherapy results in responses less than 10%. Chemotherapy always results in side effects with the risk of a low quality of life. Endocrine therapy is used world-wide among chemo-resistant ovarian cancer. Tamoxifen is a standard palliative treatment in many centers. LH-RH (luteinizing hormone-releasing hormone) agonists have also demonstrated activity among patients with ovarian cancer in several studies with response rates of 9-12% and disease stabilization in 15-26% of these women. METHODS: In this retrospective study 32 patients with ovarian cancer who had relapsed after platinum/paclitaxel-based first-line chemotherapy and had exhausted all standard treatments received LH-RH analogue Leuprorelin depot 3.75 mg sc once a month until tumor progression. RESULTS: One patient (3%) had a complete response, with remission time over 3 years. Two patients (6%) reached partial response with remission time of 3 and 4 months. Four patients (12%) remained stable for a mean time of 7 months (range 4-12 months). The remaining 25 patients (78%) had progressive disease. The treatment was well tolerated, and no major toxicity has been reported. CONCLUSION: This study showed that LH-RH agonist Leuprorelin has only a limited effect in patients pretreated with platinum-based chemotherapy.     

Phase II trial of weekly docetaxel for patients with relapsed ovarian cancer who have previously received paclitaxel--ANZGOG 02-01

OBJECTIVE: To determine the response rate of weekly docetaxel in women with relapsed epithelial ovarian cancer previously treated with paclitaxel and at least one line of platinum-based chemotherapy. METHODS: In this multi-center phase II trial, 37 patients with relapsed disease were enrolled and treated with weekly docetaxel at 35 mg/m for 5 out of 6 consecutive weeks. Two patient cohorts were considered, those who progressed or relapsed within 4 months (N=7) or at greater than 4 months (N=30) from the time of completing their last course of paclitaxel. RESULTS: Patients in both cohorts received a median of 2 cycles of treatment (range; 1-4). In evaluable patients, the combined overall response rate, using both CA125 and RECIST response criteria was 18.9% (7/37; 95% CI; 10-34%). The combined overall progression-free survival was 3.1 months (95% CI; 2.5-3.8), and the combined overall survival was 12.3 months (95% CI; 8.2-16.4). Treatment was generally well tolerated with the only grade 4 toxicity being skin toxicity (3%). The most common grade 3 toxicities were fatigue (14%) and watery eyes (8%) with grade 3 neutropenia observed in only 5% of patients. CONCLUSION: Weekly docetaxel is well tolerated and has activity in patients with relapsed ovarian cancer previously treated with platinum and paclitaxel.     

Significance of multi-drug-resistant proteins in predicting chemotherapy response and prognosis in epithelial ovarian cancer

OBJECTIVES: To clarify the expression of multi-drug-resistant (MDR) markers, GST-pi, c-Jun, P-glycoprotein (Pgp), and MDR-associated protein (MRP) in epithelial ovarian cancer, and to determine whether their expression is predictive of chemotherapy response and patient prognosis. METHODS: Specimens of 58 epithelial ovarian cancer cases obtained at initial surgery were studied immunohistochemically using antibodies. RESULTS: Overall positive rates in the 58 specimens were 58.6% for GST-pi, 44.8% for c-Jun, 27.6% for Pgp, and 22.4% for MRP. The 5-year disease-free survival rate was 26.0% for patients with MRP-positive tumors and 75.2% for those with MRP-negative tumors. The prognosis for those with MRP-positive tumors was significantly poorer (p < 0.05). Patients with GST-pi-positive tumors had a significantly worse prognosis than those with GST-pi-negative tumors (51.9% vs 79.2%, p < 0.05). Multivariate analysis showed that residual tumors 2 cm or larger and MRP expression were independent prognostic factors for chemotherapy resistance. The relative risk of chemotherapy resistance in a patient with a residual tumor 2 cm or larger, positive MRP, and positive GST-pi was 10.6 times greater than the risk in a patient without these factors. CONCLUSION: MRP and GST-pi expression might be potential predictors of the response to standard chemotherapy in epithelial ovarian cancer. Their expression also might contribute to individualizing clinical trials of postoperative chemotherapy.     

白蛋白结合型紫杉醇联合铂类或异环磷酰胺治疗复发性卵巢癌的疗效及安全性分析

目的:观察白蛋白结合型紫杉醇联合铂类或异环磷酰胺治疗复发性卵巢癌的临床疗效及毒副反应。方法:回顾分析我院46例复发性卵巢癌患者接受含不同制剂紫杉醇的联合化疗的疗效及安全性。26例铂敏感复发患者分别采用白蛋白结合型紫杉醇或溶剂型紫杉醇联合铂类化疗,20例铂耐药复发患者采用白蛋白结合型紫杉醇或溶剂型紫杉醇联合异环磷酰胺方案,每21天为1疗程,直至完全缓解后再巩固2个疗程或疾病进展或出现不可耐受的不良反应。比较患者间临床效果、毒副作用及预后差异。结果:铂敏感复发患者中,白蛋白结合型紫杉醇组的完全缓解率显著高于溶剂型紫杉醇组(60%vs 18.8%,P0.05);两组的客观缓解率分别为90%、75%。铂耐药复发患者中,白蛋白结合型紫杉醇组的完全缓解率显著高于溶剂型紫杉醇组(16.7%vs 0%,P0.05);两组的客观缓解率分别为66.7%、57.1%。铂敏感复发患者中,白蛋白结合型紫杉醇组及溶剂型紫杉醇组的中位无进展生存时间(PFS)分别为10.25、7.5个月(P0.05);铂耐药复发患者中白蛋白结合型紫杉醇组及溶剂型紫杉醇组的中位PFS分别为7.8、5.6个月(P0.05)。4组患者的不良反应主要表现为骨髓抑制和胃肠道反应,铂敏感、铂耐药患者中白蛋白结合型紫杉醇组及溶剂型紫杉醇组各种严重不良反应的发生率均无显著差异。结论:与溶剂型紫杉醇比较,含有白蛋白结合型紫杉醇的联合化疗方案治疗铂敏感或铂耐药复发性卵巢癌均有更高的完全缓解率,可有效延长PFS,且不额外增加严重毒副反应的发生率。     

卵巢上皮性癌序贯化疗41例临床分析

目的探讨卵巢上皮性癌不同化疗方案的序贯化疗效果。方法回顾性分析1998年1月-2007年11月肿瘤细胞减灭术后规范化疗的卵巢上皮性癌患者41例,其中序贯化疗组11例,应用化疗方案为TP和／或CAP和／或IAP;常规化疗组30例,应用化疗方案为TP或CAP,比较化疗毒性反应、反应率、无疾病进展期和总生存时间。结果①两组在年龄、病理类型、临床分期、组织分化程度和术后残留病灶方面差异无统计学意义（P〉0．05）;②序贯化疗组的完全缓解率（CR）、部分缓解率（PR）和总缓解率（CR＋PR）分别为57．1％、23．8X和81．oH,常规化疗组的CR、PR和CR＋PR分别为55．3％、23．4％和78．7％,组间比较,差异无统计学意义（P〉0．05）;③序贯化疗组中位无疾病进展和中位总生存时间分别为41个月和60个月,常规化疗组分别为30个月和59个月,较常规化疗组延长,但差异无统计学意义（P〉O．05）;④序贯化疗组发生3～4级白细胞减少症4例,占36．36％,常规化疗组发生10例,占33．33％,组间比较,差异无统计学意义（P〉0．05）;非血液系统化疗毒性反应主要为神经系统毒性反应,序贯化疗组发生3～4级神经系统毒性反应1例（9．09％）,常规化疗组6例（20％）。结论序贯化疗可延长卵巢癌患者的无疾病生存期,且毒性反应减少,有待今后进一步研究后用于卵巢癌一线化疗。