顺铂腹腔热灌注联合紫杉醇对晚期上皮性卵巢癌患者血清肿瘤标志物、免疫指标水平和预后的影响分析

目的 观察顺铂精准持续循环腹腔热灌注化疗(IPHC)联合紫杉醇治疗晚期上皮性卵巢癌(EOC)的疗效及对患者血清中血管内皮生长因子(VEGF)、可溶性B7H4蛋白表达和预后的影响。方法 选取2019年1月至2021年12月湖南中医药大学第一附属医院收治的104例晚期EOC患者作为观察对象,以随机余数法分为观察组与对照组各52例,对照组行常规静脉化疗,观察组行精准持续循环腹腔热灌注化疗(IPHC)联合静脉化疗。对比两组治疗6个周期后(126 d)的临床效果,比较治疗前、治疗126 d后两组肿瘤标志物【糖类抗原125(CA125)、癌胚抗原(CEA)、甲胎蛋白(AFP)、人附睾上皮分泌蛋白4(HE4)】、血清学指标【碱性成纤维细胞生长因子(bFGF)、VEGF、可溶性B7H4蛋白】、T淋巴细胞亚群指标的变化情况,统计两组治疗期间并发症的发生率。结果 治疗126 d后,观察组治疗OR率高于对照组(P <0.05);治疗后,两组各肿瘤标志物(CA125、CEA、AFP、HE4)、血清相关因子(bFGF、VEGF、B7H4)及CD8⁺水平均降低,且观察组低于对照组(P ...     

化疗免疫“窗口期”对卵巢癌治疗影响的实验研究

目的:采用荷瘤动物模型经化疗联合被动免疫治疗,初步探讨化疗免疫"窗口期"对卵巢癌免疫应答的影响及其可能的免疫学机制。方法:以荷瘤大鼠为研究对象,根据紫杉醇联合卡铂对荷瘤鼠免疫功能改变的不同时期给予CTL(cytotoxic T-lymphocyte)主动免疫治疗。观察荷瘤体积及机体免疫微环境改变。结果:荷瘤鼠紫杉醇和卡铂化疗后不同时期给予CTL转输治疗,其中化疗后第6天即淋巴细胞数最少期,给予免疫治疗,肿瘤生长最缓慢;CT扫描结果示,化疗后6天+免疫治疗组的瘤体积最小,且与其余治疗组有统计学意义。荷瘤鼠免疫功能示,化疗后6天+免疫治疗组中淋巴细胞抗原特异性增殖及CD8+T细胞最明显,而Treg(T-Lymphocytes,Regulatory)细胞明显降低。结论:紫杉醇和卡铂联合CTL治疗肿瘤具有协同作用,其中化疗后6天(即淋巴细胞降到最低期)是CTL免疫治疗的最佳时间点。化疗造成的肿瘤个体免疫功能的低下或是免疫系统空间的释放(所谓的免疫"窗口期")为诱导特异性的抗肿瘤免疫应答提供了可能,免疫状态的检测是保证肿瘤患者化疗联合免疫治疗方案治疗有效性的重要前提之一。     

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。     

白蛋白结合型紫杉醇与紫杉醇脂质体治疗晚期和复发子宫颈癌患者的临床疗效对照研究

目的:将白蛋白结合型紫杉醇联合顺铂应用于晚期和复发子宫颈癌患者的治疗,探讨其临床应用价值。方法:选择解放军总医院妇产科2015年1月至2018年1月期间诊治的晚期和复发子宫颈癌患者作为研究对象,采用前瞻性队列研究,根据化疗方案不同分为两组,观察组(n=52)采用白蛋白结合型紫杉醇+顺铂的治疗方案,对照组(n=49)采用紫杉醇脂质体+顺铂的治疗方案,比较两组的疗效和不良反应发生情况。结果:观察组的客观缓解率高于对照组[35例(67.3%) vs 23例(46.9%),P0.05];两组疾病稳定、疾病进展和疾病控制率比较差异无统计学意义(P0.05);观察组治疗费用高于对照组(25138.8±3540.7元 vs 14971.6±1633.5元,P0.05)。观察组骨髓抑制[20例(38.5%) vs 31例(63.3%)]、周围神经症状[3例(5.8%) vs 11例(22.4%)]和过敏反应[0例(0) vs 4例(8.2%)]的Ⅲ～Ⅳ级不良反应发生率低于对照组,差异均有统计学意义(P0.05);两组肝功能损害、肾功能损害和胃肠道反应的Ⅲ～Ⅳ级不良反应发生率比较差异无统计学意义(P0.05)。结论:白蛋白结合型紫杉醇与顺铂联合用于治疗晚期和复发子宫颈癌,其疗效和安全性较紫杉醇脂质体联合顺铂更有优势,但昂贵的费用是其推广使用最大的障碍。     

紫杉醇联合卡铂对荷瘤鼠细胞免疫功能影响的研究

目的:揭示紫杉醇联合卡铂对荷瘤大鼠免疫系统的影响,探讨化疗后是否存在免疫功能逆转的"窗口期"。方法:取25只Fischer 344大鼠,随机分为5组,取4组于右腋下种植NuTu-19卵巢癌细胞株,待荷瘤体积生长至0.5cm3后,以牺牲大鼠的时间为第0天,取3组分别于-15天(化疗晚期)、-10天(化疗中期)、-6天(化疗早期)在荷瘤的大鼠腹腔内注射紫杉醇、卡铂。流式细胞技术检测化疗后各时期淋巴细胞数量及刺激活化后外周血Tc1淋巴细胞的功能亚群,H3-TdR掺入法检测化疗后淋巴细胞的增殖。结果:荷瘤鼠与正常大鼠相比,淋巴细胞数量无显著差异,荷瘤组淋巴细胞亚群CD3+T、CD4+T、CD8+T、NK细胞下降,但仅CD3+T细胞较正常组有差异(P<0.05)。荷瘤组肿瘤抑制性Treg细胞明显增高(P<0.05),而具有杀伤功能的Tc1细胞在荷瘤组明显下降(P<0.05),NK的杀伤功能在两组间无显著差异。移植瘤大鼠化疗后免疫功能变化:(1)在用药后不同阶段淋巴细胞数呈先下降后逐渐恢复至正常的变化规律,在化疗后6天降到最低点,15天恢复至化疗前水平;(2)化疗后6天淋巴细胞降到最低,其增殖力最强;(3)化疗后机体外周血中CD3+T、CD4+T、CD8+T细胞、肿瘤抑制性Treg细胞绝对数均先下降后恢复,化疗后6天降到最低,较未化疗组均有统计学意义,化疗后10天开始恢复,化疗后15天均恢复到化疗前水平;(4)化疗后CD8+T细胞中Tc1细胞比例逐渐增高,化疗后6天较未化疗组增高且有统计学意义,化疗后15天达到最高,但较化疗后6天无显著性差异,表明化疗促进具有杀伤功能Tc1的表达。结论:荷瘤鼠的机体呈负调节免疫状态,肿瘤的发生引起了免疫功能的逃逸,肿瘤的免疫治疗应该具有针对性;紫杉醇联合卡铂打破机体内原有的抗肿瘤免疫抑制状态,机体有可能通过免疫重建诱生了增强的抗肿瘤免疫应答,从而使抗肿瘤免疫抑制状态得到暂时逆转,表明机体经化疗后存在免疫"窗口期"。     

甲磺酸阿帕替尼治疗晚期卵巢癌对患者人附睾蛋白4、血清甲胎蛋白及糖类抗原125的影响研究

目的 探讨甲磺酸阿帕替尼治疗晚期卵巢癌对患者人附睾蛋白4(HE₄)、血清甲胎蛋白(AFP)、糖类抗原125(CA125)水平的影响。方法 选取64例晚期卵巢癌患者,按照随机数字表法分为两组,各32例。对照组予以紫杉醇及卡铂治疗,研究组在对照组基础上加用甲磺酸阿帕替尼治疗。对比两组临床疗效、肿瘤标志物水平、生存质量及不良反应发生情况。结果 研究组疾病控制率93.75%较对照组的71.88%高,治疗后HE₄、AFP、CA125水平均较对照组低,生存质量评分较对照组高(P<0.05)。两组不良反应发生率对比差异无统计学意义(P>0.05)。结论 甲磺酸阿帕替尼可提高晚期卵巢癌控制效果,降低肿瘤标志物水平,改善患者生存质量。     

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...     

肿瘤标志物预测卵巢癌预后的价值

对卵巢癌预后进行准确预测是个体化治疗的基础和推动力。无论蛋白还是非编码RNA,都有作为卵巢癌预后预测因子的潜能。已经研究证实其中的一些肿瘤标志物与卵巢癌的总生存、无进展生存和（或）化疗反应性密切相关,但在用于临床之前还需要进一步验证。     

以卡铂加紫杉醇作为一线化疗后仍有小残留灶的卵巢癌对拓普特肯的疗效

晚期卵巢癌行彻底减瘤术后通常选用卡铂/顺铂加紫杉醇方案化疗。经此一线方案化疗后仍有20％～30％病例有小的残留灶需要进一步处理。Ⅱ和Ⅲ期临床研究显示:拓普特肯(topotecan)对包括使用铂类治疗失败的卵巢癌病例有效。将其用于经卡铂加紫杉醇治疗后仍有残留灶的晚期卵巢癌患者。 为探讨拓普特肯疗效及毒性。将其选择使用一线化疗药物(标准的卡铂加紫杉醇方案)治疗后经剖腹术或腹腔镜证实有小的残留灶(直经<2cm),组织学证实为上皮性卵巢癌     

紫杉醇脂质体联合卡铂同步放化疗治疗中晚期宫颈癌的疗效观察

目的 研究中晚期宫颈癌患者采用紫杉醇脂质体联合卡铂方案同步放化疗的临床治疗效果。方法 选取30例中晚期宫颈癌患者作为研究对象,按照随机数字表法分为试验组与对照组,每组15例。对照组应用紫杉醇联合卡铂方案同步放化疗,试验组应用紫杉醇脂质体联合卡铂方案同步放化疗。观察比较两组患者治疗3个月后的临床效果,治疗6个月后的肿瘤复发情况、无瘤生存情况,以及治疗后毒副反应发生情况。结果 试验组患者治疗3个月后的临床有效率为93.33%,明显高于对照组的60.00%,差异有统计学意义（P<0.05）。试验组患者治疗6个月肿瘤复发率为6.67%,明显低于对照组的40.00%,无瘤生存率（66.67%）明显高于对照组的26.67%,差异均有统计学意义（P<0.05）。试验组患者的毒副反应发生率为53.33%,与对照组的46.67%比较,差异无统计学意义（P>0.05）。结论 对于中晚期宫颈癌患者应用紫杉醇脂质体联合卡铂方案同步放化疗,可以显著提升患者的临床疗效和无瘤生存率,降低肿瘤复发率,且不良反应可耐受,临床应用价值较高。     

Effects of paclitaxel on CA-125 serum levels in ovarian cancer patients

OBJECTIVE: As in vitro activation of ovarian carcinoma cells in terms of CA-125 secretion by taxanes has been demonstrated, we were interested in whether taxanes also modulate CA-125 expression in vivo. METHODS: Serum CA-125 was determined immediately before and 24 h after paclitaxel-containing chemotherapy in 53 ovarian carcinoma patients. To test the quality of the analysis methods and the biological variation of untreated patients, serum CA-125 levels of two control groups were analyzed. RESULTS: Median CA-125 concentration was 107 kU/liter 24 h after chemotherapy treatment compared with 99 kU/liter the day before paclitaxel treatment. Changes in CA-125 serum levels observed immediately after paclitaxel treatment were not correlated to treatment response. However, overall change in CA-125 serum concentration was a good predictor of response to paclitaxel containing treatment. Patients achieving a complete or partial response had a significant reduction of median CA-125 levels, whereas tumor progression was associated with increased CA-125 levels. Only for the group of patients obtaining a complete response was a decrease in the median relative CA-125 value observed. CONCLUSION: Paclitaxel-induced modulation of CA-125 expression could not be confirmed in vivo.     

Phase II study of carboplatin followed by sequential gemcitabine and paclitaxel as first-line treatment for advanced ovarian cancer

The aim of this exploratory phase II study was to evaluate sequential chemotherapy with carboplatin followed by gemcitabine-paclitaxel combination in chemonaive patients with advanced ovarian cancer. The primary objective was to evaluate time to progressive disease (TTPD); secondary objectives included the evaluation of 1- and 3-year survival, response rates, and toxicity. Following initial debulking surgery or biopsy, patients with FIGO stage IIC-IV disease received four cycles of carboplatin area under the curve (AUC) 6 (day 1) every 21 days, followed by four cycles of gemcitabine 1000 mg/m(2) (days 1 and 8) and paclitaxel 175 mg/m(2) (day 8) every 21 days. A total of 47 patients enrolled, 44 (93.6%) completed the initial four cycles, and 39 patients (82.9%) completed the planned eight cycles. The median and maximum lengths of follow-up were 31.2 and 43.7 months, respectively. Median TTPD was 13.8 months (95% CI, 11.6-21.0 months), and median survival time was 31.2 months (95% CI, 25.2-39.6 months). Survival at 1 and 3 years was 95.7% and 44.2%, respectively. Of the 43 evaluable patients, most (95.3%) of them achieved a CA-125 marker response based on Gynecologic Cancer Intergroup (GCIG) definition. The partial response rate in the seven patients with measurable disease was 46.4%. Myelosuppression was the major toxicity, with grade 3 and 4 neutropenia observed in 76.6% patients and thrombocytopenia in 12.8% patients. The sequential approach of carboplatin followed by gemcitabine-paclitaxel as first-line treatment for patients with ovarian cancer is feasible and well tolerated, and depending upon the findings from other major trials, it may merit further evaluation.     

Weekly and monthly regimens of paclitaxel and carboplatin in the management of advanced ovarian cancer. A preliminary report on side effects

Abstract. Wu CH, Yang CH, Lee JN, Hsu SC, Tsai EM. Weekly and monthly regimens of paclitaxel and carboplatin in the management of advanced ovarian cancer. A preliminary report on side effects.
This preliminary study was carried out over 18 months to evaluate whether the side effects in patients with advanced ovarian cancer receiving chemotherapy using paclitaxel-carboplatin differed between weekly (98 cycles in 14 patients) and monthly (102 cycles in 15 patients) administrations. We used paclitaxel (60 mg/m²) and carboplatin (AUC of 2) in the weekly regimen and 175 mg/m² of paclitaxel and carboplatin (AUC of 6) in the monthly regimen. All eligible patients received at least four cycles of treatment in both regimens. The results revealed significantly decreased hematological toxicity in weekly regimens relative to monthly ones, ie, 7.1% vs. 18.6% of anemia (≥ grade 2), 7.1% vs. 32.3% of grade 3/4 granulocytopenia, and 0% vs. 15.7% of >grade 2 thrombocytopenia. There was no significant difference in nonhematological toxicities between the two regimens. The incidence of unscheduled events was much less in the weekly regimen than in the monthly one; ie, delayed treatment (3 vs. 18 events), unanticipated hospitalizations (3 vs. 15 times), and supplemental support with G-CSF (7 vs. 33 times). Complete responses were observed in 6 of 14 patients in the weekly regimen and in five of 15 patients in the monthly regimen, while partial responses were seen in four and five patients in the weekly and monthly regimens, respectively. The present results demonstrate that the weekly regimen can achieve the benefits of tolerable toxicity with significantly reduced myelosuppression and improved cost-effectiveness in terms of unscheduled events.     

Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study

We have previously shown that interferon-gamma 1b (IFN-gamma) in combination with cyclophosphamide and cisplatin significantly prolongs progression-free survival in ovarian cancer. In this phase I/II study, we examined if administration of IFN-gamma is also safe in combination with the current standard treatment, paclitaxel and carboplatin. Thirty-four patients with newly diagnosed advanced epithelial ovarian cancer, FIGO stage III/IV, were treated for six to nine cycles with paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] 5) every 3 weeks. IFN-gamma was administered in an escalating dose from 6 days/cycle with 0.025 mg sc up to 9 days/cycle with 0.1 mg sc. As expected, administration of IFN-gamma was associated with flu-like symptoms. Grade 3/4 neutropenia was observed in 74% (25 out of 34) of patients. Other side effects, in particular peripheral neuropathies, were within the previously observed ranges for the paclitaxel plus carboplatin combination. Overall response rate (complete or partial response) in patients who received either six or nine doses (0.1 mg) of IFN-gamma/cycle (n = 28) was 71%. IFN-gamma is safe in combination with carboplatin and paclitaxel for first-line treatment of patients with advanced ovarian cancer. This combination should be further evaluated as an immunotherapeutic treatment option for ovarian cancer.     

Prognostic value of serial CA125 measurements during chemotherapy for patients with advanced ovarian cancer

Serum CA125 concentrations measured before and during chemotherapy may provide additional information for prognostic assessment of patients with epithelial ovarian cancer (EOC), and enable discrimination between patients who are likely to benefit from further therapy and those who will not. Medical records of 40 patients with advanced EOC, treated at the Department of Obstetrics and Gynecology of the University Hospital Nijmegen between July 1984 and April 1993, were examined. All patients had primary cytoreductive surgery followed by platinum-based chemotherapy. Serum samples were obtained before surgery and during chemotherapy. Follow-up information and patient and tumor characteristics were abstracted from medical records until December 1, 1994. By using multivariate Cox proportional hazards models for disease-free and overall survival it was evaluated whether outcome prediction was improved by inclusion of serum CA125 quantitations.
  Only FIGO stage and extent of residual tumor were significant independent prognostic factors before the start of chemotherapy. When such regression models were constructed after subsequent courses of chemotherapy, serum CA125 measurements conducted after each of the first three chemotherapy courses improved the prediction of disease-free survival. Prediction of overall survival was improved by inclusion of serum CA125 measurements after courses 1–6. Inclusion of serum CA125 measurements during chemotherapy improved prognostic assessment of patients with advanced EOC.     

Developmental chemotherapy in advanced ovarian cancer: Incorporation of topoisomerase-I inhibitors and perspective of the Gynecologic Oncology Group

Abstract. Bookman MA. Developmental chemotherapy in advanced ovarian cancer: Incorporation of topisomerase-I inhibitors and perspective of the Gynecologic Oncology Group.
Despite improvements in median and overall survival using a combination of platinum and paclitaxel, long-term survival rates for patients with advanced epithelial ovarian carcinoma (EOC) remain disappointing, and the development of more effective primary therapy remains a priority. In particular, several interesting chemotherapy agents have demonstrated activity individually in patients with recurrent EOC. Among these are gemcitabine, topotecan, liposomal doxorubicin, and prolonged oral etoposide. Preclinical models have suggested an advantage for combinations of these agents with platinum, which has been attributed to inhibition of DNA synthetic pathways involved in the repair of platinum-DNA adducts. However, efforts to develop multidrug combinations with platinum and paclitaxel have encountered substantial bone marrow toxicity, prompting exploration of alternative schedules and sequences of drug administration. In this regard, the Gynecologic Oncology Group (GOG) has conducted a series of phase I pilot studies in previously untreated patients to define combinations that are suitable for group-wide phase III trials. With international collaboration, GOG has launched a five-arm trial (GOG-0182) that will compare these combinations against carboplatin-paclitaxel. The selection of candidate regimens for this trial illustrate the challenges of drug development in EOC.