经皮肝动脉栓塞化疗治疗卵巢上皮癌肝转移瘤的初步研究

目的 :探讨治疗卵巢上皮癌 (EOC)肝实质内转移瘤的新方法。方法 :6例EOC肝实质内转移的患者 ,接受经动脉插管栓塞化疗 (TACE)和静脉化疗。治疗后定期行CT或MRI检查和CA12 5水平测定 ,根据治疗前后CA12 5水平和CT或MRI所测肿瘤体积的变化和生存时间评价治疗效果。结果 :平均随访时间 18.3个月 (9～ 38个月 ) ,4例生存 ,2例死亡。其中显效 1例、有效 2例、稳定 1例和恶化 2例 ;CA12 5正常 4例、下降 2例。结论 :TACE治疗EOC肝实质转移是有效的 ,为EOC肝实质转移提供了一种新的治疗方法。     

卵巢上皮癌不同治疗方法及影响预后的因素分析

本研究回顾性分析我院收治的 2 12例卵巢上皮癌患者的不同治疗方式及影响预后的因素。1　资料与方法　　 2 12例均为大连市妇产医院妇科 1990年 5月至 1995年 5月间收治的卵巢上皮癌患者。其病理切片由我院病理科同一医生复查核实。临床分期以国际妇产科联盟 (ＦＩ ＧＯ) 1988年推荐的卵巢癌手术病理分期法为标准。患者年龄为 17～ 70岁 ,平均年龄为 (48 7± 1 2 )岁。浆液性癌12 8例占 6 0 4 % ,其中Ⅰａ及Ⅰｂ期 2 4例 ,Ⅰｃ期 39例 ,Ⅱ期 11例 ,Ⅲ期及Ⅳ期患者 5 4例 ;粘液性囊腺癌 36例 ,Ⅰａ及Ⅰｂ期 6例 ,Ⅰｃ期 11例 ,Ⅱ期 2例 ,Ⅲ…     

复发性卵巢上皮癌的处理

目的　探讨复发性卵巢癌复发的相关因素和二次肿瘤细胞减灭术的作用。方法　采用回顾性分析方法对我院 1 990年 1月～ 2 0 0 0年 1 2月收治的 2 1例复发性卵巢癌患者的治疗、复发、生存情况进行总结。结果　初次手术后残留癌灶直径≤ 2cm组与残留癌灶直径 >2cm组的平均复发时间分别为 2 8 9个月和 1 4 8个月 ,差异有显著性 (P <0 0 5 )。初次手术后进行C (A)P方案化疗与TP方案化疗的复发比例分别为 1 4 6 9(2 0 2 9% )和 7 1 8(38 89% ) ;初次手术 1年内化疗≥ 6疗程者与 <6疗程者的平均复发时间分别为 2 3 1个月和1 5个月 ,差异均无显著性 (P >0 0 5 )。二次肿瘤细胞减灭术及仅接受化疗的复发癌患者的平均生存时间分别为4 3个月和 1 9个月 ;2年生存率分别为 71 4 %和 2 8 6 % ,差异有显著性 (P <0 0 5 )。结论　初次手术后残留癌灶的大小、初次手术 1年内化疗疗程是复发的相关因素。复发癌二次肿瘤细胞减灭术与单纯化疗相比 ,可延长患者的生存时间。     

血清CA125预测卵巢上皮癌治疗后复发的Meta分析

目的:系统评价血清CA125对卵巢上皮癌综合治疗(手术+化疗)后复发的诊断价值。方法:计算机检索Pub Med、EMBASE、Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CJFD)、中国科技期刊数据库(CSJD)、中国知网(CNKI)数据库,检验医学专业数据库:IFCC循证实验医学数据库、Medion、CRDdatabase、Bandlier Knowledge library等;灰色文献检索:中国学术会议论文库(CACP)、ISTP,检索期限自建库至2015年12月31日。收集有关血清CA125诊断卵巢上皮癌综合治疗后复发的前瞻性或回顾性队列研究。使用诊断性试验准确性质量评价工具(QUADAS)评价文献质量并提取数据,采用Meta-Disc1.4版软件进行Meta分析。结果:共纳入33篇文献,共2188例患者。Meta分析结果显示,血清CA125对卵巢上皮癌治疗后复发的诊断优势比DOR为11.77(95%Cl为7.16~19.37),灵敏度为67%(95%Cl为65%~70%),特异度为83%(95%Cl为80%~85%),阳性似然比为3.83(95%Cl为2.70~5.43),阴性似然比为0.41(95%Cl为0.35~0.49)。结论:血清CA125阴性排除"卵巢癌复发"的价值较大,而阳性诊断"卵巢癌复发"的价值有待进一步确证。     

肿瘤细胞减灭术在治疗Ⅳ期卵巢上皮癌中的作用

Ⅳ期卵巢上皮癌患者存在盆腔外转移病灶,尚无公认的理想治疗方案.在Ⅳ期卵巢癌中肿瘤细胞减灭术能达到理想程度,并在延长生存期和改善生活质量方面有积极意义.手术的范围应视病人的具体情况而定,并尽可能使术后残留灶＜2cm.为达到Ⅳ期卵巢癌满意的肿瘤细胞减灭术应强调术前改善患者的全身情况和行先期化疗以利于手术切净肿瘤.     

复发性卵巢上皮癌治疗中几个问题的探讨

卵巢癌确诊时70%已属晚期,治疗困难,虽经数十年努力,但治疗效果仍在原地徘徊。至今有关卵巢癌的治疗仍有一些问题未达统一。手术治疗的时间、方法、切除范围、淋巴清扫、大网膜切除范围、肠管病灶处理、复发者再次手术、手术与化疗配合等有许多问题未臻一致。所以还需要共同探索,更需以充分的实践和理论依据来阐述有关问题。以百花齐放、百家争鸣的原则,既借鉴国外经验,也有我国自己的经验,以期对患者有益,使医疗水平进一步提高。为此,本刊开辟《学术争鸣》栏目,请妇产科同道积极参与。本文是探讨有关卵巢上皮癌复发患者手术治疗问题,希望能对卵巢癌的治疗有所裨益。     

晚期卵巢癌卡铂、紫杉醇二联方案与表柔比星联合应用的研究

旨在改善晚期卵巢癌一线化疗药物的疗效，德国AGO-OVAR设计了联合卡铂、紫杉醇和表柔比星的三联疗法（TEC），联合法国GINECO开展Ⅲ期随机试验，比较TEC化疗方案和卡铂、紫杉醇（TC）方案对晚期卵巢上皮癌的疗效。     

白介素-2联合化疗治疗卵巢上皮癌腹水23例临床分析

卵巢癌合并腹水的治疗是临床上较棘手的，随着近年来发病率的增高，卵巢癌合并腹水越来越常见，为了使更多的晚期患者延长生存时间，减少痛苦，我们采用了白介素-2（IL-2）联合化疗治疗中晚期卵巢上皮癌23例，取得了非常好的疗效，现报告如下。     

c-Met和MMP-2在卵巢上皮癌中的表达及相关性研究

目的探讨肝细胞生长因子受体(c-Met)和基质金属蛋白酶-2(MMP-2)在卵巢上皮癌中的表达特点及生物学行为关系。方法应用免疫组化S-P法检测50例卵巢上皮癌、15例交界性卵巢上皮肿瘤、20例良性卵巢上皮肿瘤及20例正常卵巢组织中c-Met和MMP-2的表达情况。结果 c-Met和MMP-2在卵巢上皮癌中的阳性表达率分别为84.0%和86.0%,与卵巢上皮癌的组织分化和临床分期有关,而与组织类型无关。c-Met和MMP-2表达具有正相关性(P0.05)。结论 c-Met和MMP-2的表达可能与卵巢上皮癌的发生发展有关,c-Met和MMP-2表达呈正相关,二者可成为观察卵巢上皮癌侵袭进展、转移和预后的指标。     

CA125测定联合B超检查对卵巢上皮癌的诊断和预后的价值分析

目的　探讨CA1 2 5检测联合B超检查在卵巢上皮癌的诊断及预后的价值。方法　卵巢上皮癌、卵巢良性肿瘤术前进行CA1 2 5测定和B超检查 ,卵巢上皮癌者术后 1周及每次化疗前复查CA1 2 5和B超。结果　术前卵巢上皮癌的CA1 2 5明显高于卵巢上皮癌术后组及卵巢良性肿瘤组 ,Ⅲ、Ⅳ期卵巢上皮癌的CA1 2 5明显高于Ⅰ、Ⅱ期 ;2 7%的CA1 2 5>6 0 0U/ml患者能施行理想的肿瘤细胞减灭术。CA1 2 5联合B超使卵巢上皮癌的诊断阳性率提高达 95 %。结论　CA1 2 5是卵巢上皮癌诊断和判断预后的特异性指标 ,CA1 2 5联合B超检查可提高卵巢上皮癌的诊断率。     

First-line chemotherapy with epidoxorubicin,paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients

OBJECTIVE: A combination of carboplatin (CBDCA) and paclitaxel (TAX) is the standard treatment in advanced ovarian cancer (AOC) patients. Epidoxorubicin (EDX) is an active treatment in AOC and exhibits nonoverlapping toxicities with CBDCA and TAX; moreover, when added to platinum-based chemotherapy, it improves long-term survival. We have therefore conducted a phase II study to evaluate the tolerability and antitumor activity of an EDX/TAX/CBDCA (ETC) triplet in AOC patients. METHODS: Patients with histologically confirmed suboptimal stage III-IV ovarian cancer who had not previously received cytotoxic drugs were treated with TAX (175 mg/m(2) in a 3-h iv infusion), CBDCA (AUC 6, Calvert formula), and EDX (75 mg/m(2) iv bolus) all given on day 1 every 28 days for a maximum of six courses on an outpatient basis. EDX dosage was chosen after a pilot phase I study. RESULTS: Fifty-five patients were registered, of whom 5 were determined ineligible bacause of age. Forty-two of the 50 are evaluable for response; 27 (64%) achieved a clinical complete response (CR) and 9 (21%) a partial response (PR) for a response rate of 86% (95% CI 71-94%). Thirty-three patients underwent a secondary debulking procedure after a median of 6 courses (range 2-6). Pathological CR and PR were observed in 9 (27.3%) and 21 (63.6%), respectively; among patients with persistent disease a successful cytoreduction (<1 cm) was obtained in 53.8% of patients. At a median follow up of 35.6 months (range 0-55.5) median progression-free survival is 19.5 months and median overall survival is 36 months. The most common adverse effects were G3-4 leukopenia and thrombocytopenia which occurred in 59 and 37% of patients, respectively. CONCLUSIONS: The ETC combination given according to the outlined doses and schedule is highly active in AOC patients with poor prognostic factors and deserves further study.     

Secondary leukemia after treatment with paclitaxel and carboplatin in a patient with recurrent ovarian cancer

Abstract.   See HT, Thomas DA, Bueso-Ramos C, Kavanagh J. Secondary leukemia after treatment with paclitaxel and carboplatin in a patient with recurrent ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 236–240.
The occurrence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) has been reported after treatment with cytotoxic alkylating agent–based chemotherapy for solid tumors. We report a patient with metastatic ovarian carcinoma treated with carboplatin and paclitaxel, who developed secondary acute erythroid leukemia. The overall survival of patients with stage III and IV ovarian cancer has increased in the past decade. Monitoring of the long-term outcome of paclitaxel- and platinum-based regimens is warranted, particularly with regard to monitoring the development of secondary MDS and/or AML. The incidence and outcome of secondary leukemia in the setting of active ovarian carcinoma is reviewed.     

The search for biomarkers to direct antiangiogenic treatment in epithelial ovarian cancer

Antiangiogenic agents have demonstrated improved progression-free survival in women with primary and recurrent epithelial ovarian cancer (EOC). Biomarkers that predict outcomes in patients treated with antiangiogenic agents are being investigated to rationally direct therapy for women most likely to benefit from these agents. Among the most promising plasma-based biomarkers are vascular endothelial growth factor (VEGF)-A, fibroblast growth factor, platelet-derived growth factor, angiopoietin-2, and VEGF receptor-2. While these biomarkers have been correlated with prognosis, they have not been shown to predict benefit, specifically from anti-VEGF therapy, highlighting the need for alternative biomarkers, including molecular and clinical factors, which may be predictive of outcome in women with ovarian cancer treated with antiangiogenic agents. Biomarkers are currently being investigated as secondary outcomes in several ongoing phase II and phase III clinical trials of antiangiogenic agents in patients with EOC. Molecular techniques, such as microarray analyses, and imaging techniques, such as dynamic contrast-enhanced magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, are also being explored in this field. In this review, we provide a comprehensive overview of current biomarker research, with an emphasis on angiogenic biomarkers associated with EOC.     

A phase I study of paclitaxel, topotecan, cisplatin and Filgrastim in patients with newly diagnosed advanced ovarian epithelial malignancies: a Gynecologic Oncology Group study

OBJECTIVES: To determine a recommended dose level (RDL) of paclitaxel, cisplatin and topotecan in women with previously untreated epithelial ovarian or peritoneal cancer as a possible experimental arm in a future Gynecologic Oncology Group phase III study. METHODS: Patients with newly diagnosed stage III or IV disease were treated with paclitaxel 175 mg/m2/3 h, followed 2 h later by cisplatin 50 mg/m2 on day 1. Topotecan was administered on consecutive days as a 30-minute infusion, beginning after cisplatin on day 1, receiving either 5 days beginning at 0.3 mg/m2 (cohort 1), or 3 days beginning at 0.5 mg/m2 (cohort 2). Treatment was given every 21 days for a maximum of 8 cycles. RESULTS: Forty-five evaluable patients were enrolled in the two cohorts. Thrombocytopenia and prolonged neutropenia were the major dose-limiting toxicities. Dose-limiting neutropenia was seen at the first dose level, thus all subsequent dose escalations included Filgrastim. The RDL of cohort 1 was paclitaxel 175 mg/m2/3 h, cisplatin 50 mg/m2 and topotecan 0.5 mg/m2 daily x 5 with Filgrastim. The RDL of cohort 2 was paclitaxel 175 mg/m2/3 h, cisplatin 50 mg/m2 and topotecan 0.75 mg/m2 daily x 3 with Filgrastim. CONCLUSION: In women with previously untreated epithelial ovarian or peritoneal cancer the combination of paclitaxel, cisplatin and topotecan is feasible. However, this treatment requires the use of Filgrastim and attenuated dosing of topotecan in both a 5-day and 3-day topotecan infusion schedule.     

Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer

OBJECTIVE: Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. METHODS: Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0-2 and normal bone marrow, renal and hepatic function. 25 patients (age 18-75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m(2) via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. CONCLUSION: Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.     

MAGE-A family serves as poor prognostic markers and potential therapeutic targets for epithelial ovarian cancer patients: a retrospective clinical study

Objective: The aim of our study is to investigate the expression pattern and prognostic significance of melanoma-associated antigens-A (MAGE-A) family in primary epithelial ovarian cancer (EOC) patients.

Study design: The expression of MAGE-A family members, including MAGE-A1, -A2, -A3, -A4, -A6, -A10 and -A12 was immunohistochemically detected in 82 cases of primary EOC and 10 cases of pericarcinoma ovarian tissues. The association between MAGE-A family expression and the clinicopathological parameters as well as the prognosis of primary EOC patients was analyzed.

Results: MAGE-A family expressed in 48.8% of primary EOC tissues, but not expressed in pericarcinoma ovarian tissues. MAGE-A expression was associated with the pathological types, FIGO stage, and pre-operative serum CA125 level. Overall survival of EOC patients with positive MAGE-A family expression was significantly shorter than those patients with negative MAGE-A expression. Multivariate analysis showed that although MAGE-A family expression can affect the overall survival, it was not an independent prognostic marker for EOC patients.

Conclusions: Molecular assessment of MAGE-A family members could be helpful to improve the prognostic evaluation and to provide a new potential therapeutic target for primary EOC patients.     

Randomized phase II trial of carboplatin and paclitaxel with or without lonafarnib in first-line treatment of epithelial ovarian cancer stage IIB-IV

Objectives

This study evaluates whether a molecular targeted therapy with the farnesyltransferase inhibitor lonafarnib added to standard chemotherapy in first-line treatment of advanced ovarian cancer (OC) could improve progression-free (PFS) and overall survival (OS).

Patients and Methods

We performed a prospective randomized phase II study to compare standard therapy carboplatin (C; AUC 5) and paclitaxel (T; 175 mg/m²) in primary advanced OC with or without lonafarnib (L). Lonafarnib was given in a dose of 100 mg orally twice a day during chemotherapy and was increased afterwards to 200 mg up to six months as a maintenance therapy.

Results

105 patients were recruited (53 patients were randomized to receive LTC, 52 to TC). Hematologic toxicity was similar in both arms. Grade 3 and 4 non-hematological toxicity, occurred significantly more often with LTC (23% versus 4%, p = 0.005) and was associated with a higher dropout rate. PFS and OS were not significantly different among both arms. The LTC arm showed inferiority in the stratum with residual tumor of more than 1 cm: median PFS was 11.5 months (95% CI: 7.4-14.2) compared with 16.4 (95% CI: 10.3-40.4) for TC (p = 0.0141; HR = 0.36 (95% CI: 0.15-0.84)) with median OS 20.6 months (95% CI: 13.1-31.0) and 43.4 months (95% CI: 15.7-) for the TC arm (p = 0.012; HR = 0.32 (95% CI: 0.13-0.8)).

Conclusion

The addition of lonafarnib did not improve PFS or OS. Patients with a residual tumor of more than 1 cm had significantly shorter PFS and OS. Incorporation of lonafarnib into future studies for primary therapy of OC is not recommended.