白蛋白结合型紫杉醇在妇科肿瘤中的研究进展

白蛋白结合型紫杉醇是一种以白蛋白为溶剂的新型紫杉醇制剂,相对于传统紫杉醇制剂（溶剂为聚氧乙烯蓖麻油和无水乙醇）,其抗肿瘤能力更强且血液毒性、严重过敏反应等毒副作用更小。近几年来,白蛋白结合型紫杉醇应用范围越来越广泛,其在妇科肿瘤中的临床研究也相继开展。分别为单药白蛋白结合型紫杉醇应用于铂类敏感及耐药型的复发性卵巢癌、腹膜癌和输卵管癌;白蛋白结合型紫杉醇联合贝伐单抗治疗铂类抵抗或铂类难治的复发性卵巢癌、腹膜癌和输卵管癌,结果显示白蛋白结合型紫杉醇疗效明显且不良反应可耐受。白蛋白结合型紫杉醇在复发或转移性中晚期宫颈癌中的Ⅱ期临床研究结果显示,白蛋白结合型紫杉醇是一种值得考虑且不良反应小的药物。总的来说,有关白蛋白结合型紫杉醇在妇科肿瘤中的临床研究相对较少,需进一步研究。     

白蛋白结合型紫杉醇与溶剂型紫杉醇在卵巢癌新辅助化疗中的疗效分析

目的 对比白蛋白结合型紫杉醇和溶剂型紫杉醇在卵巢癌患者新辅助化疗过程中的疗效,以期为卵巢的治疗及预后提供依据。方法 将2014年8月至2019年8月在哈尔滨医科大学附属肿瘤医院妇一科住院的208例卵巢癌患者随机分为白蛋白结合型紫杉醇组(104例)和溶剂型紫杉醇组(104例)。白蛋白结合型紫杉醇组给予白蛋白结合型注射用紫杉醇260mg/m²静脉滴注治疗;溶剂型紫杉醇组卵巢癌患者则给予紫杉醇注射液175mg/m²静脉滴注治疗。两组患者均连续治疗3个疗程,观察两组患者一般特征、随访结果、不良反应情况及卵巢癌标志物表达水平。结果 白蛋白结合型紫杉醇组患者癌性腹水(65.4%vs. 84.6%)和淋巴结转移(19.2%vs. 34.6%)发生率、化疗前肿瘤相关标志物CA125(44.9%vs. 55.1%)、肿瘤细胞增殖指数Ki67(29.5±20.16 vs. 35.71±20.0)表达水平均低于溶剂型紫杉醇组患者(均P<0.05)。结论 白蛋白结合型紫杉醇的疗效较好,不良反应发生率更低,更适合用于卵巢癌的新辅助化疗。     

紫杉醇联合铂类治疗持续耐药及复发性妊娠滋养细胞肿瘤的疗效分析

目的:评价紫杉醇联合铂类药物化疗方案治疗持续耐药及复发性妊娠滋养细胞肿瘤(GTN)患者的疗效及安全性。方法:回顾性分析2006年1月至2013年1月,在北京协和医院接受紫杉醇联合铂类化疗方案治疗的25例持续耐药及复发性GTN患者的治疗情况及最终治疗结局。结果:25例持续耐药及复发性GTN患者共接受了115疗程的紫杉醇联合铂类的化疗方案,平均每例4.6±2.2(2~10)疗程,具体包括紫杉醇+顺铂(TP)方案52疗程、紫杉醇+卡铂(TC)方案56疗程及紫杉醇+依托泊苷/紫杉醇+顺铂(TE/TP)方案7疗程。在停止化疗时,血清学完全缓解14例,部分缓解4例,治疗无效7例,完全缓解率为56.0%(14/25),总缓解率为72.0%(18/25),血清学完全缓解后的复发率为35.7%(5/14),平均复发时间为95.4±18.4天(约3.2个月)。紫杉醇联合铂类方案的毒副反应主要为骨髓抑制、消化道反应、肝肾损伤及过敏等,发生Ⅲ~Ⅳ度骨髓抑制患者比例为48.0%,未发生致死性副反应。结论:紫杉醇联合铂类对持续耐药及复发性GTN患者是可供选择的化疗方案。     

多西他赛联合奈达铂治疗复发性浆液性卵巢癌的疗效观察

目的研究多西他赛联合奈达铂治疗复发性上皮性卵巢癌的疗效及其安全性。方法回顾性分析34例复发性上皮性卵巢癌患者,根据实体肿瘤治疗疗效评估标准(RECIST)和血清CA125水平评估多西他赛联合奈达铂化疗方案的疗效,并依据WHO抗癌药物毒性表现及分级标准评估其安全性。结果 34例患者在完成2个化疗疗程后,完全缓解10例(29.4%),部分缓解10例(29.4%),病情稳定9例(26.5%),进展5例(14.7%),总有效率58.8%,疾病控制率85.3%。主要不良反应为轻度骨髓抑制及胃肠道反应。结论多西他赛联合奈达铂化疗方案治疗复发性上皮性卵巢癌,无论铂类敏感或耐药,均有较好的疗效,且不良反应相对轻微。     

雷替曲塞联合奈达铂对复发性子宫颈癌的疗效及不良反应初探

目的:探讨复发性子宫颈癌采用雷替曲塞与奈达铂联合治疗的临床效果及不良反应。方法:选择2016年6月至2018年12月在中国医科大学附属盛京医院妇产科收治的复发性子宫颈癌患者39例进行回顾性分析,按照化疗方案不同分为观察组(采用雷替曲塞联合奈达铂方案化疗)9例和对照组(采用紫杉醇联合顺铂或卡铂方案化疗)30例,比较两组临床疗效及不良反应情况。结果:①观察组和对照组客观有效率(ORR)分别为77.8%(7/9)和76.7%(23/30),疾病控制率(DCR)分别为88.9%(8/9)和86.7%(26/30),无进展生存期(PFS)中位数分别为12.3±2.2个月和11.3±1.4个月,生活质量改善率分别为88.9%和83.3%,两组比较差异无统计学意义(P0.05)。②在不良反应分级中,观察组白细胞发生Ⅲ～Ⅳ级下降率(0)明显低于对照组(6.7%),观察组均出现轻度白细胞下降,而对照组40.0%出现下降,两组白细胞下降率的分布比较,差异有统计学意义(P0.05)。两组其他不良反应发生率的分布比较,差异无统计学意义(P0.05)。结论:雷替曲塞联合奈达铂治疗复发性子宫颈癌安全、有效,其疗效与紫杉醇联合顺铂或卡铂化疗疗效相近,但白细胞下降增多,其他不良反应无差异。     

复发性上皮性卵巢癌的治疗

对复发性上皮性卵巢癌的处理一直是二分棘手和被关注的课题。手术加化疗仍是复发性卵巢癌的主要治疗方法，包括二次肿瘤减灭和二线化疗。复化性癌分为铂敏感和铂耐药肿瘤二大类。对铂敏感肿瘤再次采用铂为基础化疗仍可产生高的疗效；对铂耐药肿瘤可选用目前较有效的紫杉醇、异环磷酰胺和六甲密胺。     

奈达铂联合紫杉醇脂质体或多西他赛治疗复发性卵巢癌的疗效观察

目的 探究奈达铂联合紫杉醇脂质体或多西他赛治疗复发性卵巢癌的疗效。方法 回顾性分析江苏省苏北人民医院2020年2月至2022年2月收治的85例复发性卵巢癌患者的临床资料,根据其治疗方案分为奈达铂联合紫杉醇脂质体治疗组（A组, 41例）及奈达铂联合多西他赛治疗组（B组, 44例）。分别记录两组铂类敏感型和铂类耐药型患者的临床疗效,比较两组患者的总体临床疗效、毒副反应及治疗前、治疗2个疗程后肿瘤标志物[糖类抗原125(CA125)、癌胚抗原(CEA)]水平;并采用Kaplan-Meier法绘制1年生存曲线,使用Logrank法比较两组患者的1年生存率差异。结果 A组铂类敏感型和铂类耐药型患者临床疗效比较,差异无统计学意义（P>0.05）。B组铂类敏感型患者临床疗效高于铂类耐药型患者（P <0.05）。两组总体临床疗效、毒副反应及1年生存率比较,差异均无统计学意义（P>0.05）。治疗2个疗程后,两组血清CA125、CEA水平均较治疗前降低（P <0.05）;但两组组间比较,差异无统计学意义（P>0.05）。结论 奈达铂联合紫杉醇脂质体或联合多西他赛治疗复发性卵...     

白蛋白结合型紫杉醇与紫杉醇脂质体治疗复发性卵巢癌近期疗效与安全性分析

目的:探讨白蛋白结合型紫杉醇(PTX)与PTX脂质体(力扑素)治疗复发性卵巢癌的近期疗效及不良反应。方法:回顾性分析采用PTX治疗的90例复发性卵巢癌患者的临床资料,其中应用白蛋白结合型PTX联合奈达铂治疗30例为PTX结合型组,应用PTX脂质体联合奈达铂治疗60例为PTX脂质体组。比较两组癌抗原125(CA125)下降情况和肿瘤病灶缩小情况,以及不良反应的差异。结果:PTX结合型组CA125下降的有效率(63.3%)高于PTX脂质体组(41.7%);PTX结合型组病灶缩小的有效率(54.5%)高于PTX脂质体组(23.8%),差异均有统计学意义(P0.05)。PTX结合型组腹泻、呕吐、白细胞减少Ⅲ~Ⅳ级的不良反应发生率均少于PTX脂质体组(P0.05),两组神经毒性发生率比较,差异无统计学意义(P0.05)。结论:白蛋白结合型PTX联合奈达铂与PTX脂质体联合奈达铂治疗复发性卵巢癌相比,其临床近期疗效提高,严重不良反应率较低,使用方便,值得推广。     

复发性卵巢癌治疗新进展

卵巢癌是妇科肿瘤中死亡率居首位的肿瘤,传统的治疗方法为肿瘤细胞减灭术的基础上联合药物(铂类和紫杉醇为主的)化疗,近年治疗方法的进步使越来越多的患者得到完全缓解,但最终大多患者会复发。复发后存活时间一般少于3年。复发性卵巢癌主要的治疗方法仍是化疗(铂敏感型仍采用铂类为基础的化疗,铂耐药型则多认为使用非铂类药物)和手术(二次肿瘤细胞减灭术)。以肿瘤发病机制为基础的靶向治疗方法近年成为研究热点,进一步研究基因和信号转导途径将为治疗该病提供新途径。现就近年各种治疗方法的有效性和安全性做一综述。     

复发性上皮性卵巢癌临床治疗进展

上皮性卵巢癌(epithelial ovarian cancer,EOC)患者如初次就诊时已为晚期,虽然肿瘤细胞减灭术和术后辅以紫杉醇/铂类为基础的联合化疗可使大部分患者获得临床缓解,但最终仍有80%的患者复发。复发性EOC的治疗原则是姑息而不是治愈,生存质量是再次治疗时考虑的重要因素。可根据患者初次手术情况及术后化疗方案及途径、疗效、毒副反应、复发类型等制定个体化的治疗方案,以缓解、控制症状、提高患者的生存质量及延长无进展生存期。对于仅限于单个病灶复发或手术能达到有效减瘤程度的倾向于减瘤术联合化疗,对那些大块而广泛甚至伴有远处转移的更倾向于只进行化疗。在制定方案时,常把耐药型、顽固型和难治型患者归为一组,鼓励其进行新药临床试验或接受非铂类制剂化疗;对敏感型推荐以铂类或铂类加紫杉醇为基础的化疗方案。生物治疗作为肿瘤治疗的另一种治疗模式日益受到重视,成为传统手术治疗和化疗的有力补充。     

The "Leuven" dose-dense paclitaxel/carboplatin regimen in patients with recurrent ovarian cancer

OBJECTIVE: The purpose of this study was to evaluate the "Leuven" dose-dense regimen in recurrent ovarian cancer. METHODS: Six courses of paclitaxel (90 mg/m(2)) and carboplatinum (AUC 4) on d1 and d8 every 3 weeks were administered. Response rates were determined using RECIST and Gynaecological Cancer Intergroup (GCIG) CA 125 criteria. Platinum resistance was defined as progression during or within 6 months after platinum-based chemotherapy. RESULTS: Thirty-three patients were included with a median number of prior treatment regimens of 2. Nine patients were platinum-resistant and 24 were platinum-sensitive. Three of 8 patients in the platinum-resistant group and 16 of 21 patients in the platinum-sensitive group achieved an evaluable response according to RECIST. According to the GCIG CA 125 criteria 3 of 7 patients in the platinum-resistant and 17 of 19 patients in the platinum-sensitive patients responded. In the entire patient population evaluable for response (n=29), the median progression-free survival (PFS) was 9 months; the median overall survival (OS) was 18 months. Median PFS was 6.75 months for the platinum-resistant and 10.5 months for the platinum-sensitive group. The median OS was 8 months in the platinum-resistant and not yet reached in the platinum-sensitive group. Toxicity was mostly bone marrow-related with neutropenia grade 3/4 in 34% and neutropenic fever in 2% of courses. Dose reduction was necessary in 25% of patients. Nausea and vomiting and fatigue were the most frequent non-hematological side effects. CONCLUSION: Dose-dense paclitaxel and carboplatin offers a well-tolerated regimen with high response rates even in heavily pre-treated and platinum-resistant ovarian cancer.     

Weekly low-dose carboplatin and paclitaxel in the treatment of recurrent ovarian and peritoneal cancer

OBJECTIVES: Weekly paclitaxel alone has moderate activity in the salvage treatment of recurrent ovarian cancer and is associated with a favorable toxicity profile. Combination paclitaxel and carboplatin is a well-established first-line regimen for ovarian cancer. The purpose of this study was to evaluate weekly low-dose paclitaxel and carboplatin in recurrent ovarian or peritoneal cancer. METHODS: Patients with recurrent ovarian or peritoneal cancer previously treated with between one and four chemotherapeutic regimens were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA-125 greater than 75 U/ml. One cycle of treatment consisted of carboplatin at an area under the curve of 2 and paclitaxel at 80 mg/m(2) on days 1, 8, and 15 on a 28-day cycle. Clinical responses were defined by established criteria. RESULTS: Twenty-nine patients were included in this intent-to-treat study. The median number of prior treatment regimens was 2 (range 1 to 4). The overall response rate was 82.8% (16 complete clinical responses, 8 partial responses). Among 8 platinum-refractory patients, the response rate was 37.5%, while 21 platinum-sensitive patients had a 100% response rate. Median time to progression was 13.7 months among platinum-sensitive patients and 3.2 months among platinum-refractory patients. Overall median time to progression was 11.5 months and median-duration of response was 9.9 months. Hematologic toxicity was common (32% grade 3 neutropenia, no grade 4 neutropenia, 14.2% grade 3 or 4 thrombocytopenia) and managed by treatment delay, dose reduction of paclitaxel, or discontinuation of carboplatin. CONCLUSION: Weekly low-dose carboplatin and paclitaxel has significant activity in both platinum-sensitive and platinum-resistant recurrent ovarian cancer with acceptable toxicity that is easily managed by dose adjustment.     

Dose-dense chemotherapy with weekly paclitaxel and 3-weekly carboplatin for recurrent ovarian cancer

ObjectiveTo analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review.Materials and methodsPatients accepted weekly paclitaxel 80 mg/m² on day 1, 8, 15 and carboplatin on day1 at area under curve (AUC) 6 every 21 days were reviewed for the response rate, progression-free survival, overall survival, and toxicity during January 2012 to April 2016 in Chang Gung Memorial Hospital at Linkou, Taiwan.ResultsSixteen patients with recurrent ovarian cancer, including 1 platinum-resistant, 7 partially platinum-sensitive, and 8 platinum-sensitive, accepted a median of 6 cycles of chemotherapy (range 3–10). The overall response rate (ORR) and complete response (CR) rate were 93.8%, and 62.5%, respectively. The median PFS of all patients were 10.9 months (range 4.3–40.5). The median time to response (TTR) was 29.0 days (range 19.6–38.4). The median disease-free survival (DFS) after CR was 5.6 months (range 1.2–34.2). Grade 3 at least toxicity included anemia (6.3%), neutropenia (50%), and thrombocytopenia (18.8%).Twenty-nine articles on phase I, II, III, or retrospective studies of dose-dense chemotherapy with weekly paclitaxel were reviewed.ConclusionThis is the first report using Japanese Gynecologic Oncology Group 3016 protocol, weekly paclitaxel and 3-weely carboplatin, on recurrent ovarian cancer. The current study showed high ORR and CR with tolerable toxicities. Our study suggested dose-dense chemotherapy with paclitaxel, especially combining carboplatin created high efficacy probably by anti-angiogenesis. However, consolidation or maintenance therapy is needed to prolong DFS.     

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.     

Gemcitabine in epithelial ovarian cancer treatment: current role and future perspectives

Newer agents and combinations are needed in order to improve current results in ovarian cancer treatment. Gemcitabine is a novel agent that has shown consistent activity as a single agent in the treatment of platinum-resistant ovarian cancer and a favorable toxicity profile. Because of its clinical and preclinical synergism with platinum analogs, gemcitabine has been combined with carboplatin as a convincing approach in the treatment of platinum-sensitive recurrent ovarian cancer patients. Further combination of gemcitabine and other agents, including paclitaxel, is also feasible and has been actively studied in order to establish the role of gemcitabine in the management of treated and untreated ovarian cancer patients.     

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。     

Ifosfamide and vinorelbine in advanced platinum-resistant ovarian cancer: excessive toxicity with a potentially active regimen

OBJECTIVES: The aim of this study was to determine the activity and toxicity of a vinorelbine and ifosfamide combination in platinum-resistant advanced ovarian cancer. PATIENTS AND METHODS: Patients were treated with ifosfamide (2 g/m(2)/day) infused over 1 h x 3 days (with mesna uroprotection) and vinorelbine (30 mg/m(2)) on days 1 and 8. Treatment was repeated on a 21-day schedule. In order to avoid unacceptable toxicity in this subset of patients where the chemotherapy is mainly palliative, the Bryant and Day two-stage phase II trial design incorporating toxicity considerations was chosen. A cutoff point for the response rate (10%) and for severe toxicity (25%) was established for the first 14 patients. RESULTS: Between February 1997 and December 1998, 11 paclitaxel and platinum-resistant patients and 1 potentially platinum-sensitive patient were treated. Five patients (41%) experienced grade 3-4 central nervous toxicity requiring hospital admission. In accordance with the Bryant and Day design, the study was stopped early because greater than 25% of the first 14 patients developed grade 3-4 neurotoxicity. A retrospective review of clinical characteristics of these patients showed at least one well-known risk factor associated with ifosfamide central toxicity. Hematological toxicity was common, mainly grade 4 neutropenia, which was observed in all but 1 patient, usually of short duration, and there were 4 episodes of neutropenic fever. Ten patients were evaluated for response. Two complete responses and 1 partial response according to CA-125 criteria were observed. CONCLUSION: This combination may be active in platinum-resistant ovarian cancer but the high toxicity encountered, principally neurotoxicity in those with large central pelvic masses, means that further studies with this schedule may not be warranted.     

Treatment of relapsed carcinoma of the ovary with single-agent paclitaxel following exposure to paclitaxel and platinum employed as initial therapy

OBJECTIVES: The aim of this study was to evaluate the ability of paclitaxel to achieve a second clinical response in patients with recurrent epithelial ovarian carcinoma who responded to standard therapy with platinum and paclitaxel in the initial setting. METHODS: Thirty-four patients with epithelial ovarian who demonstrated a complete response to paclitaxel and platinum in the initial treatment setting were retreated with paclitaxel as a single agent for relapse of their disease. Paclitaxel was given at a dose of 135-175 mg/m(2) over 3 h at 21-day intervals. Fifteen patients had platinum-resistant disease and 19 had potentially platinum-sensitive disease. Response was documented by physical examination, serial serum CA125 measurement, or radiologic evaluation. RESULTS: An objective response to paclitaxel retreatment was demonstrated in 15 patients (44%), with a median progression-free interval (PFI) of 8.6 months (range 4-17 months). An additional 14 patients (41%) demonstrated disease stabilization, with a median PFI of 7.4 months (range 3-13 months). Overall, retreatment with paclitaxel was well tolerated, with minimal cumulative toxicities, despite repetitive dosing. CONCLUSION: These results demonstrate that patients with ovarian cancer who relapse after initial treatment with paclitaxel often have disease that is still responsive to the agent. Given its relative lack of cumulative toxicity, retreatment with paclitaxel as a single agent is a reasonable therapeutic option for patients with recurrent ovarian cancer.     

卵巢癌靶向治疗的规范化

近年来靶向治疗在卵巢癌领域取得了较大进展，改变了卵巢癌的治疗模式。贝伐珠单抗在高危晚期卵巢癌的初始治疗和维持治疗中、在铂敏感和铂耐药复发性卵巢癌的治疗中有确切疗效，可与化疗联合，也可单独应用。聚腺苷二磷酸核糖聚合酶（poly ADP-ribose polymerase，PARP）抑制剂是目前卵巢癌靶向治疗中最重要的一类药物，通过“合成致死”效应发挥抗肿瘤作用，显著改善了卵巢癌患者的预后，已作为标准治疗推荐用于初治晚期卵巢癌的一线维持治疗和铂敏感复发性卵巢癌的维持治疗。靶向治疗在严格掌握适应证的同时，应重视规范化的全程管理，包括用药前评估、用药期间和用药后的监测及不良反应的及时处理，以减少和减轻不良反应的发生，增加长期用药安全性，同时也可提高患者的依从性，这也是保障疗效的基础。