Paclitaxel–Anthracycline Combination Chemotherapy in Relapsing Advanced Ovarian Cancer after Platinum-Based Chemotherapy: A Pilot Study

Despite high response rates with platinum-based front-line chemotherapy, the prognosis for advanced ovarian carcinoma (AOC) is poor. Salvage chemotherapy for recurrent AOC was of little benefit before paclitaxel as single-agent therapy showed appreciable efficacy. Anthracyclines are effective, but are not often part of first-line therapy. In this pilot study, we investigated the feasibility of an anthracycline plus paclitaxel combination therapy for recurrent AOC. Twenty-four patients received 150 mg/m²paclitaxel on day 1, with either 50 mg/m²doxorubicin on day 1 or 75 mg/m²epirubicin on day 1 every 3 weeks. A 27% overall response rate was obtained. Myelosuppression was the major toxicity, but was manageable. No myocardiac toxicity was observed. We conclude that paclitaxel–anthracyclines is a promising salvage combination therapy in AOC that should be investigated further.     

Paclitaxel and Cisplatin Combination Chemotherapy in Recurrent Epithelial Ovarian Cancer

The objective of this study was to assess the efficacy of chemotherapy in recurrent epithelial ovarian cancer using the sequential combination of 24-hr paclitaxel followed by cisplatin. All patients presenting to the Department of Gynecologic Oncology at Roswell Park Cancer Institute between April 1993 and May 1995 with recurrent epithelial ovarian cancer were offered enrollment in a prospective trial utilizing paclitaxel 135 mg/m²administered in a continuous 24-hr intravenous infusion, followed by intravenous cisplatin 50 mg/m². Forty-nine patients were entered into the study. Of 38 patients evaluable for response, there were 14 complete responders and 6 partial responders for an overall response rate of 53%. Median survival was >23 months for responders and 12 months for the entire study group. All complete responders were still alive with a median follow-up of 23 months. Of 12 evaluable patients whose tumors had progressed on single-agent paclitaxel, 4 achieved an objective response with the addition of cisplatin. Response rates and survival were similar in patients with platinum-resistant tumors compared to patients with platinum-sensitive tumors, and in patients who had received one, two, or multiple prior chemotherapy regimens. The combination of paclitaxel administered in a 24-hr infusion followed by cisplatin is highly active in recurrent epithelial ovarian cancer, even in patients who have previously failed single-agent paclitaxel or cisplatin-based chemotherapy.     

Options for Primary Chemotherapy in Advanced Ovarian Cancer: The European Perspective

Primary chemotherapy for ovarian cancer has evolved over the past 30 years from the use of single alkylating agent to several combination regimens. Treatment strategies, however, vary greatly both nationally and internationally, since no firm results can be derived from available data. Five questions can be identified: (1) Should primary chemotherapy consist of single agent or combination? (2) Should it include doxorubicin? (3) Is cisplatin or carboplatin preferred? (4) Which is the role of cisplatin dose intensity? (5) Should it include taxol? Available data from the European experience are discussed. Final considerations include: (1) Platinum combinations are more effective than single agent platinum when this drug is used at the same dose (now considered lower than current standard). (2) CAP offers a survival benefit of 7% at 6 years compared to CP. However, in most trials dose intensity was higher in CAP than in CP. (3) Cisplatin and carboplatin are equally effective. (4) There is no survival benefit when doubling the dose intensity of cisplatin over 25 mg/m²/week. (5) A confirmatory study will help define the contribution of Taxol in the first-line treatment of ovarian cancer, when administered at 175 mg/m² over a 3-hr infusion in association with cisplatin.     

原发性卵巢平滑肌肉瘤诊断和治疗(附2例报告)

目的探讨原发性卵巢平滑肌肉瘤的临床特点及诊断、治疗方法.方法对2例原发性卵巢平滑肌肉瘤进行临床报告及分析.结果原发性卵巢平滑肌肉瘤可发生在任何年龄,临床表现不典型.诊断主要依靠病理,核分裂数为主要依据,同时结合免疫组化Desmin(-),Vimentin(+)诊断.结论原发性卵巢平滑肌肉瘤恶性度高,预后差,治疗需以手术为主,辅以合适的放疗和化疗综合性治疗.     

Comparison of Platinum-based Neoadjuvant Chemotherapy and Primary Debulking Surgery in Patients with Advanced Ovarian Cancer

Purpose

Ovarian cancer is the sixth common cancer in women in developed countries. In severe cases, the optimal debulking is necessary. In order to increase optimal debulking and reduce preoperative complications, neoadjuvant chemotherapy followed by debulking surgery, and then chemotherapy again is introduced as substitute for primary surgery. In this study, we aim to evaluate perioperative outcome after neoadjuvant chemotherapy with carboplatin/paclyaxol in comparison with primary cytoreduction in patients with advanced ovarian cancer.

Methods

In this prospective study, 60 patients with advanced ovarian cancer due to the disease severity were assigned into neoadjuvant chemotherapy (n = 30) or control (n = 30) groups. In neoadjuvant chemotherapy group, patients received three cycles of carboplatin (5–6 area under the curve) and paclitaxel (175 mg/m²) preoperatively followed by interval surgery. The control group received primary surgery plus adjuvant chemotherapy. Preoperative outcome was compared between groups.

Results

Neoadjuvant group had significantly lower mean levels of CA 125 (p = 0.01) and less severe bleeding (p = 0.03) than control group. There was no significant difference between surgery time, preoperative complications, residual mass less than 1 cm, and hospital stay between groups. There was no mortality during the study.

Conclusion

Neoadjuvant chemotherapy caused less severe bleeding, but has no effect in decreasing complications after surgery; however, neoadjuvant chemotherapy followed by interval debulking surgery was not superior to primary debulking surgery followed by chemotherapy as a treatment option for patients with advanced ovarian carcinoma in this study.     

抗血管生成药物联合化疗在复发性卵巢癌治疗中的研究进展

卵巢癌是妇科常见的恶性肿瘤之一,其发生、发展及肿瘤细胞的浸润转移离不开新生血管,因此通过抑制肿瘤新生血管形成,是治疗卵巢癌的有效途径之一。目前主要研究的抗血管生成药物包括血管内皮生长因子抑制剂(如贝伐单抗)、酪氨酸激酶抑制剂(如索拉菲尼、帕唑帕尼、西地尼布等)和血管生成素抑制剂(如Trebananib)。大量的Ⅱ、Ⅲ期临床试验表明抗血管靶向药物联合化疗为复发性铂敏感性或铂耐药性卵巢癌的治疗带来了曙光,明显延长了疾病无进展生存期。综述不同抗血管靶向药物联合化疗治疗复发性卵巢癌的临床研究现状及最新进展。     

卵巢原发恶性淋巴瘤的诊断与治疗

恶性淋巴瘤侵及女性生殖系统比较罕见,仅1％的患者表现为卵巢首发。卵巢原发恶性淋巴瘤的临床表现易与晚期卵巢癌混淆,术前不容易诊断,一般仅靠手术后的病理确诊。近年随着腹腔镜技术和病理诊断技术的开展,各种生物标志物的发现,针对恶性淋巴瘤的个案报道较多。卵巢原发恶性淋巴瘤多通过腹腔镜探查术见卵巢肿瘤的组织活检获得病理诊断。可针对组织学分型进行相应的化疗或放疗。针对近年卵巢原发恶性淋巴瘤的诊断与治疗综述。     

卵巢原发恶性淋巴瘤的诊断与治疗

恶性淋巴瘤侵及女性生殖系统比较罕见,仅1%的患者表现为卵巢首发.卵巢原发恶性淋巴瘤的临床表现易与晚期卵巢癌混淆,术前不容易诊断,一般仅靠手术后的病理确诊.近年随着腹腔镜技术和病理诊断技术的开展,各种生物标志物的发现,针对恶性淋巴瘤的个案报道较多.卵巢原发恶性淋巴瘤多通过腹腔镜探查术见卵巢肿瘤的组织活检获得病理诊断.可针对组织学分型进行相应的化疗或放疗.针对近年卵巢原发恶性淋巴瘤的诊断与治疗综述.     

化疗对卵巢功能及生育功能影响研究进展

化疗造成的卵巢功能损害是不可忽视的,但化疗对卵巢功能影响的机制尚未完全阐明。不同的化疗药物因其作用方式不同,对卵巢的影响方式也不同。化疗可致月经异常、短暂闭经、卵巢功能早衰甚至永久性闭经。目前大多数学者认为月经恢复的患者均能获得妊娠机会,但恢复月经不代表恢复生育能力。化疗后妊娠期并发症和围生儿不良结局并未明显增加。妊娠率和月经恢复情况是最直观的卵巢功能评价指标,近年来抗苗勒管激素(AMH)成为预估化疗后卵巢功能的重要指标,年龄也是卵巢储备的重要预测因子。促性腺激素释放激素激动剂(Gn RHa)对化疗中卵巢的保护作用仍存争议,不能作为保护卵巢功能的方法推荐。因此临床肿瘤医师在面对肿瘤患者时应不仅仅关注肿瘤的治疗问题,还应积极应对治疗带来的生育问题。     

Five-Year Survival after Second-Line Cisplatin-Based Intraperitoneal Chemotherapy for Advanced Ovarian Cancer

Background.To evaluate the 5-year survival rates of second-line intraperitoneal chemotherapy in advanced-staged ovarian cancer.Materials and Methods.Between August 1985 and September 1991, 63 patients with advanced epithelial ovarian cancer received intraperitoneal cisplatin and cytarabine chemotherapy as second-line treatment.Results.The median survival from the time of initiation of intraperitoneal chemotherapy (IPC) was 29.1 months. A significant advantage in 5-year survival (40%) and 5-year progression-free survival (37%) was observed among 21 patients who demonstrated a response to first-line and second-line treatment compared to those who demonstrated a response to first-line treatment only (6 and 0%, respectively) (P< 0.0001). No patient (n= 13) who failed to respond to either first-line or second-line treatment survived for 5 years. Among 42 patients with ≤5 mm residual disease at the time of initiation of IPC, 5-year survival was 36% and 5-year progression-free survival was 31%, while no patient (n= 21) with residual disease measuring >5 mm at the initiation of IPC survived 5 years (P< 0.0001).Conclusion.Given the limitation that this is not a randomized trial, the data appear to indicate that salvage platinum-based intraperitoneal chemotherapy results in significant 5-year survival and progression-free survival in selected patients who initiated therapy with small (≤5 mm) tumor burden. These survival rates as second-line therapy approach those achieved by first-line platinum-based intravenous chemotherapy in patients with advanced-stage ovarian cancer with similar small residual disease at the initiation of therapy.     

Combined Cisplatin and Carboplatin Chemotherapy for Treatment of Advanced Epithelial Ovarian Cancer

Purpose. The primary goal of this trial was to evaluate the clinical activity and the toxicity of a combination of cisplatin and carboplatin for women with advanced-stage epithelial ovarian cancer. Patients and methods. Fifty-one consecutive evaluable patients with untreated stage III and IV epithelial ovarian cancer received 360 mg/m² carboplatin on Day 1 and 50 mg/m² cisplatin on Day 2 administered intravenously every 28 days for six cycles. Drug doses were adjusted for hematologic toxicity based on nadir counts during the prior therapy course. Dose levels included 300-400 mg/m² carboplatin and 50-75 mg/m² cisplatin. Second-look surgery was optional. Endpoints were clinical response, surgical response, progression-free survival, and survival. Results. Of 8 patients with measurable disease, 3 (37.5%) had a clinical compete response, and 3 (37.5%) had a clinical partial response, for an overall clinical response rate of 75%. Of 39 patients who began chemotherapy with abnormal serum levels of CA 125, 31 (79%) achieved normalization of CA 125 at the completion of chemotherapy. Thirteen patients underwent second-look laparotomy. Of these, 7 (54%) had a pathological compete response, and 2 (15%) had a partial response. The median progression-free survival was 14 months, and the overall median survival was 32.5 months. Neutropenia and thrombocytopenia were the main dose-limiting toxicities. In addition, 9 patients developed grade 2 and 3 developed grade 3 ototoxicity. Conclusion. This regimen is very active against advanced-stage epithelial ovarian cancer. The degree of ototoxicity observed is worrisome, but such toxicity may be ameliorated by limiting the dose of cisplatin and increasing the dose of carboplatin.     

Neoadjuvant Chemotherapy or Primary Debulking Surgery in Advanced Ovarian Carcinoma: A Retrospective Analysis of 285 Patients

Objective.This study was aimed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma.Methods.Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed.Results.In the period 1980–1988 all patients underwent primary debulking surgery and 82% were cytoreduced to less than 0.5 cm largest residual tumor mass (n= 112). Analysis of this group of patients showed that some subgroups of patients (e.g., Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load. The complication rate was high especially in the group with unfavorable prognosis (postoperative mortality, 6%). In the period 1989–1997 (n= 173) the patients were surgically evaluated to receive primary chemotherapy (43%) or primary debulking surgery (57%). Prognostic variables were similar for both treatment periods. The actuarial crude survival was higher in the second time period (3-year crude survival of 26% ± 4.3 and 42% ± 4.6 for the first and second time periods, respectively;P= 0.0001). The postoperative mortality was 0% during the second time period. From 1993 on, the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinically obvious metastatic disease was made with the help of an open laparoscopy (n= 77). Median duration of the laparoscopy, blood loss, and hospital stay due to this procedure were 25 min, 10 ml, and 2 days. Primary and interval debulking surgery was performed in 36 and 63% of this subgroup of patients, respectively.Conclusion.In this retrospective analysis over two different time periods, crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery. The role of neoadjuvant chemotherapy should be evaluated in a prospective randomized study.     

Immunophenotype of Ovarian Cancer as Predictor of Clinical Outcome: Evaluation at Primary Surgery and Second-Look Procedure

Objective.This study was undertaken to evaluate whether immunophenotyping of advanced epithelial ovarian cancer could predict response to initial chemotherapy and whether tumor immunophenotype changed after chemotherapy.Study design.Fifty-four patients with stage III and IV ovarian cancer, treated at the University of Washington Medical Center, had pathology specimens evaluated. A subset of 23 patients also had specimens from a secondary surgery evaluated. Using immunocytochemistry, tumors were immunostained for overexpression of c-erb-B-2, epidermal growth factor receptor (EGFR), p53, and expression of the Ki67-defined antigen (a marker of cellular proliferation), tumor necrosis factor α (TNFα), estrogen receptor (ER), progesterone receptor (PR), and P-glycoprotein (P170, a marker of multidrug resistance). Twenty-four patients had a good response to chemotherapy (defined as a negative, or microscopically positive second look), and 30 had a poor response (defined as grossly positive second look or progressive disease).Results.Comparison of tumor markers from the initial and the secondary surgeries revealed that the only significant change was in the Ki67-defined cell proliferation rate, which showed a marked reduction in those with a good response to chemotherapy (P= 0.002). Comparison of tumor markers at initial surgery between good and poor responders revealed a correlation with p53 expression. Good responders were less likely to have p53 overexpression compared to poor responders, and this result approached significance (P= 0.058). Comparison of tumor markers at secondary surgery revealed a significant reduction in Ki67-defined cell proliferation rate in good responders compared to poor responders (P= 0.01). No significant differences were found between good and poor responders for the other tumor markers evaluated.Conclusions.The only tumor markers to predict for response to chemotherapy were p53 at initial surgery (P= 0.058) and Ki67 indices at secondary surgery (P= 0.001). Expression of steroid hormone receptors, TNFα, and P-glycoprotein and overexpression of c-erb-B-2 or EGFR are not associated with chemoresistance.     

Fertility Outcome after CO2 Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study

Study ObjectiveTo assess the postoperative likelihood of conception in patients with endometriomas managed by either CO₂ laser vaporization or cystectomy.DesignA retrospective study with prospective recording of data.SettingUniversity hospital.PatientsOne hundred and forty-two patients with symptomatic endometriomas.InterventionsPatients underwent a standardized laparoscopic stripping technique (Group 1) or cyst vaporization with CO₂ fiber laser (Group 2). Patients wishing to become pregnant were allowed to attempt a spontaneous conception after surgery. If spontaneous conception failed, patients were referred for in vitro fertilization (IVF).Measurements and Main ResultsThe primary objective was to compare pregnancy rates between the 2 groups. The secondary objective was the identification of independent predictors of pregnancy. Thirty-nine women in Group 1 (53.4%) and 39 women in Group 2 (56.5%) desired to conceive after surgery. Three patients (7.7%) in Group 1 became pregnant following donor-IVF and were excluded. Pregnancies were recorded in 72.2% of patients treated with cystectomy and in 74.3% of those managed with CO₂ fiber laser (p = .83). Twenty patients (55.6%) in Group 1 and 14 patients (35.9%) in Group 2 conceived spontaneously (p = .08). Among patients who failed spontaneous conception, 21 patients (28%) achieved pregnancy through IVF (Group 1: n = 6, 16.7%; Group 2: n = 15, 38.5%; p = .08). Twenty patients (26.7%) never became pregnant. Age at the time of surgery (odds ratio (OR) = 0.86; 95% Confidence intervals (CI): 0.78–0.96, p = .002) and duration of infertility (OR=0.80; 95% CI: 0.69–0.92, p = .006) were identified as independent indicators for pregnancy.ConclusionCO₂ laser-treated endometrioma is associated with pregnancy rates equal to those observed after cystectomy and favorable IVF outcomes. The one step CO₂ fiber laser technique may represent a viable alternative to cystectomy.     

铂类与异环磷酰胺联合化疗治疗卵巢复发癌48例临床分析

目的探索卵巢癌二线化疗方案。方法选择曾接受过肿瘤细胞减灭术及多疗程联合化疗、体检或影像学检查有可测得的肿瘤存在、一个月内无化疗史、未接受过放疗、血象及肝肾功正常、病理证实的卵巢上皮性复发癌患者作为治疗对象。用顺铂或卡铂与异环磷酰胺联合化疗,美施钠解毒。结果４８例病人中无完全缓解者;部分缓解１４例（２９２％）;稳定２２例（４５８％）;无效１２例（２５０％）。不同程度毒副反应病人可以耐受。结论顺铂或卡铂与异环磷酰胺联合化疗可作为卵巢上皮性复发癌补救治疗中的主要手段之一,且副反应病人可以耐受。     

Clostridium Difficile Diarrhoea Associated with Chemotherapy for Ovarian Cancer

EDITORIAL COMMENT: We accepted this paper for publication as it will interest readers involved with the management of gynaecological oncology patients, especially those with diarrhoea after chemotherapy. The paper makes the point that diarrhoea associated with chemotherapy may be due to Clostridium difficile, which can be effectively treated with metronidazole and should be looked for more frequently.     

针灸联合宫内人工授精(IUI)治疗多囊卵巢综合征所致不孕——65例疗效观察

目的:观察针灸与药物促排卵配合宫腔内人工授精(IUI)治疗多囊卵巢综合征(PCOS)所致不孕的临床疗效。方法:125例PCOS患者随机分为2组:治疗组65例,在药物促排卵基础上于IUI术前、后加针灸治疗;对照组60例,在IUI术前单以药物促排卵治疗。结果:治疗组的周期排卵率为83.9%,妊娠率为36.9%,黄素化未破裂卵泡(LUF)发生率为4.1%,周期取消率为6.3%;对照组周期排卵率为69.9%,妊娠率为20%,LUF发生率为23.1%,周期取消率为21.4%,组间比较均有显著差异(P<0.05或P<0.01)。结论:针灸配合IUI治疗PCOS可有效提高临床妊娠率,降低了LUF及卵巢过度刺激综合征(OHSS)等并发症的发生率。     

剂量密集化疗治疗晚期上皮性卵巢癌疗效观察

目的：探讨剂量密集化疗和标准化疗方案治疗晚期上皮性卵巢癌的临床疗效。方法：选取天津市第五中心医院院内化疗的晚期上皮性卵巢癌患者共89例,将患者随机分为剂量密集组45例和标准方案组44例,2组患者的年龄、病理分型和肿瘤临床分期差异均无统计学意义（P＞0.05）。标准方案组：紫杉醇180 mg/m2（静脉滴注维持3 h）,随后使用卡铂AUC 6（静脉滴注维持1 h,第1天）,间隔3周,共6个疗程。剂量密集组：紫杉醇80 mg/m2第1,8,15天+卡铂AUC 6（静脉滴注维持1 h,第1天）,每周期间隔3周,共6个疗程。2组进行治疗并随访3年,分别对2组患者的近期疗效、远期疗效和不良反应等进行比较。结果：剂量密集组总体缓解率高于标准方案组,差异有统计学意义（P＜0.05）;疾病无进展生存期（PFS）和3年生存率指标的比较,剂量密集组显著高于标准方案组（P＜0.01）;虽然其不良反应发生率亦高于标准方案组,但仅Ⅲ～Ⅳ级贫血发生率2组相比差异有统计学意义（P＜0.05）,其余发生率差异无统计学意义（P＞0.05）。结论：剂量密集化疗可有效提高晚期上皮性卵巢癌患者的3年生存率,延缓肿瘤复发。