卵巢癌铂耐药：PFI“二分法”的局限性与可能的改进
作者简介:
李笑宇（2001-），女，博士在读，主要从事妇产科临床与基础研究，ORCID: 0009-0002-7987-9320
张楠（1989-），女，博士，主治医师，主要从事妇科肿瘤的基础和临床研究，ORCID: 0000-0002-8996-6105
狄文: 上海交通大学医学院附属仁济医院主任医师，教授，博士生导师，上海市妇科肿瘤重点实验室主任，中国医师协会妇产科医师分会会长，中华医学会妇产科学分会副主任委员，上海市医师协会妇产科医师分会会长，上海市母婴安全专家委员会主任委员，《中华妇产科杂志》副总编，《中国实用妇科与产科杂志》和《上海医学》副主编以及多家杂志编委。担任国家卫生健康委员会住院医师规范化培训规划教材《妇产科学》、国家卫生和计划生育委员会“十三五”英文版规划教材全国高等学校教材《妇产科学》等多本教材主编。 获2010年教育部科技进步二等奖、2022年中华医学科技奖二等奖、2022年上海市科学技术奖一等奖、2018年上海医学科技奖一等奖、2009年上海医学奖二等奖及2009年上海科技进步三等奖。所编教材荣获2009年上海交通大学第十二届优秀教材特等奖、2011年上海市高校优秀教材二等奖、2015年上海普通高校优秀教材奖。2008年入选上海市科委优秀学科带头人培养计划、2011年入选上海市领军人物
。
通讯作者:
*并列第一作者
Platinum Resistance in Ovarian Cancer: Limitations of PFI Binary Classification and Potential Improvements
-
摘要:
卵巢癌是一种较为常见的妇科恶性肿瘤，临床上主要通过无铂间期将复发性卵巢癌分为铂耐药性与铂敏感性，分别对应不同的治疗方式及预后。铂耐药性卵巢癌的治疗十分困难，随着研究的深入，有学者提出根据无铂间期的“二分法”存在一定局限性。因此，本文将对复发性卵巢癌的分类、铂耐药性卵巢癌的治疗困境、无铂间期“二分法”的局限性与新的分类思路作一综述，帮助临床工作者更好地了解卵巢癌分类方面的研究进展，从而制定更加有效的治疗策略。
Abstract:Ovarian cancer is a common gynecologic malignancy. In clinical practice, recurrent ovarian cancer is mainly classified into two categories on the basis of platinum-free interval, platinum-resistant and platinum-sensitive, corresponding to different treatment modalities and prognoses. The treatment of platinum-resistant ovarian cancer is challenging. Some scholars have pointed out limitations in the binary classification of platinum-free interval. In this article, the classification of recurrent ovarian cancer, the treatment challenges of platinum-resistant ovarian cancer, the limitations of the platinum-free interval binary classification, and new classification perspectives were reviewed to help physicians enhance their understanding on the research progress in ovarian cancer classification and develop more effective treatment strategies.
-
Key words:
- Ovarian neoplasms /
- Platinum resistance /
- Platinum-free interval /
- Classification
-
0 引言
受环境污染、生活习惯改变、人口老龄化等因素的影响, 全球恶性肿瘤患者人数不断增多已成为当今阻碍人类寿命增长的主要疾病[1]。ABRAMS等对1 000例死于恶性肿瘤的患者进行尸检发现, 有494例出现肝脏转移, 肝转移性肿瘤是影响预后的重要因素[2-4]。恶性肿瘤的主要临床治疗方法有手术、放疗、化疗、靶向治疗、免疫疗法和中医治疗。化疗和放疗在抑制肿瘤细胞增殖的同时, 也会破坏机体自身的免疫功能, 进而降低肿瘤患者的生活质量[5-6]。减少肝脏转移, 减轻放化疗的不良反应, 对于提高患者的生活质量, 延长患者的生存期显得尤为重要。
中医药的整体调理, 在增强机体免疫功能、提高生活质量、减轻放化疗不良反应、抑制或延缓肿瘤进展、延长生存期等方面有着单纯西医治疗无法替代的优势。基于"扶正培本"的治疗法则, 与现代临床免疫学相结合的中西医结合治疗观念的兴起, 作为肝转移瘤综合治疗中的重要补充手段, 中成药金龙胶囊与放化疗相结合显示出良好的疗效。本研究通过对金龙胶囊联合放化疗治疗肝转移瘤的疗效进行分析和系统评价, 以期为治疗恶性肿瘤的合理化、规范化用药提供一定的循证医学证据。
1 资料与方法
1.1 文献检索
根据Cochrane指南, 对PubMed、CNKI、维普、万方和CBM数据库进行全面的检索, 检索时间从建库至2019年2月。检索词为:Jin-long capsule、liver metastases、Liver tumor、Liver cancer、hepatic secondary tumors、Liver Metastases Randomized Controlled Trials、金龙胶囊、肝转移、肝肿瘤、肝癌、肝继发瘤、肝转移瘤, 研究方法为随机对照试验, 语种不限。
1.2 文献纳入标准
(1) 随机对照临床试验; (2)患者经临床病理和细胞学检查确诊为恶性肿瘤, 并发生肝转移; (3)患者随机分为实验组和对照组, 对照组单纯进行放化疗, 实验组在放化疗的基础上口服金龙胶囊。
1.3 文献排除标准
(1) 对每篇文献都进行质量评估, 对质量评估差的文献予以剔除; (2)重复报告者, 剔除先前报道的文献; (3)非随机对照临床试验剔除; (4)研究对象基线资料不一致, 没有可比性予以剔除; (5)数据不完整、没有数据或者不能获取全文的予以剔除。
1.4 质量评价
纳入研究的文献质量由2位作者根据Cochrane系统评价手册评定。包括7方面评定依据:随机方法、分配隐藏、受试者盲法结果、评价盲法、结果数据完整性、选择性报告和其他偏倚。
1.5 统计学方法
通过Rveman5.3进行数据统计。采用卡方检验分析纳入研究间的异质性, 如果I2 < 50%, P>0.1, 表明各研究间不存在显著的统计学异质性, 采用固定效应模型; 如果I2 ≥ 50%, P≤0.1, 表明各研究间存在显著的统计学异质性, 采用随机效应模型, 并根据文献分析可能存在的异质性因素。
2 结果
2.1 研究特点
最终8个研究被纳入分析, 见图 1。其基本情况, 见表 1。
表 1 纳入研究的基本情况Table 1 Basic information of included literatures
2.2 质量评价
随机方法:纳入的8个研究均为随机对照实验, 但所有研究均未描述隐藏分组及盲法的具体方法和过程, 仅提及"随机"并未描述具体方法。结果评价盲法:8项研究均未提及结果评价盲法, 但均使用了客观指标。结果数据完整性:8项研究病例数据均完整。选择性报告:结局指标均完整纳入。纳入研究的质量评价, 见表 2。结果表明, 纳入此Meta分析的研究质量水平低, 鉴于文献质量, 有一定的偏倚风险。
表 2 纳入文献的质量评价表Table 2 Quality evaluation form of included studies
2.3 疗效
纳入的8个研究均报道了疗效, 并均采用实体瘤评判标准。异质性检验结果表明, 各研究间不存在显著性差异(χ2=4.44, P=0.73, I2=0), 采用固定效应模型进行Meta分析。结果显示, 与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤的客观有效率明显提高(RD(risk difference)=0.14, 95% CI:0.05~0.23, P=0.002), 见图 2。
![]()
图 2 单纯放化疗组与金龙胶囊联合放化疗治疗肝转移瘤疗效比较Figure 2 Comparison of therapeutic effects between chemoradiotherapy group and chemoradiotherapy combined with Jinlong capsule group on liver metastases2.4 恶心呕吐发生率
纳入的研究中有3个研究报道了恶心呕吐情况, 异质性检验结果表明各研究间不存在显著性差异(χ2=2.04, P=0.36, I2=2%), 采用固定效应模型进行Meta分析。结果显示, 与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤的恶心呕吐发生情况明显减少(OR=0.46, 95% CI:0.25~0.85, P=0.01), 见图 3。
![]()
图 3 单纯放化疗组与金龙胶囊联合放化疗治疗肝转移瘤发生恶心呕吐概率比较Figure 3 Comparison of nausea and vomiting between chemoradiotherapy group and chemoradiotherapy group combined with Jinlong capsule group on liver metastases2.5 腹痛发生率
纳入的研究中有3个研究报道了腹痛情况, 异质性检验结果表明各研究间不存在显著性差异(χ2=1.64, P=0.44, I2=0), 采用固定效应模型进行Meta分析。结果显示, 与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤的客观腹痛发生情况明显减少(OR=0.53, 95% CI:0.28~1.01, P=0.05), 见图 4。
![]()
图 4 单纯放化疗组和与金龙胶囊联合放化疗治疗肝转移瘤发生腹痛概率比较Figure 4 Comparison of abdominal pain between chemo radiotherapy group and chemoradiotherapy group combined with Jinlong capsule group on liver metastases2.6 免疫细胞含量
2.6.1 血清T细胞CD3
纳入的8篇文献中有3篇记录了治疗前后T细胞CD3含量的变化, Meta分析结果显示异质性较大(χ2=14.76, P=0.0006, I2=86%), 选用随机效应模型, 均数差(SMD合并)的合并效应量为1.86, 95% CI:0.86~2.87, 认为与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤对降低免疫系统的损伤, 帮助免疫功能恢复更有效果, 其异质性高(I2=86%), 该结论可信度较低, 见图 5。
2.6.2 血清T细胞CD4
纳入的8篇文献中有3篇记录了治疗前后T细胞CD4含量的变化。结果显示异质性较大(χ2=3.22, P=0.20, I2=38%), 选用固定效应模型, 均数差(SMD合并)的合并效应量为1.01, 95% CI:0.69~1.33, 认为与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤对降低免疫系统的损伤, 帮助免疫功能恢复更有效果, 其异质性低(I2=38%), 该结论可信度较高, 见图 6。
2.6.3 血清T细胞CD8
纳入的8篇文献中有3篇记录了治疗前后T细胞CD8含量的变化。结果显示异质性较大(χ2=15.50, P=0.0004, I2=87%), 选用随机效应模型, 均数差(SMD合并)的合并效应量为0.15, 95% CI:-0.71~1.01, 差异无统计学意义(P=0.73), 见图 7。
2.6.4 血清T细胞CD4/CD8比值
纳入的8篇文献中有3篇记录了治疗前后T细胞CD4/CD8含量的变化。结果显示异质性较大(χ2=0.72, P=0.70, I2=0), 选用固定效应模型, 均数差(SMD合并)的合并效应量为0.30, 95% CI:0.23~0.37, 认为与单纯放化疗组相比, 金龙胶囊联合放化疗治疗肝转移瘤对降低免疫系统的损伤, 帮助免疫功能恢复更有效果, 其异质性低(I2=0), 该结论可信度高, 见图 8。
2.7 发表偏倚分析
采用漏斗图评价可能存在的发表性偏倚。因有效率定量分析中包含本研究的8篇文献, 绘制漏斗图可以看出大部分研究处于"倒漏斗"的中部, 且左右大致对称, 表明发表偏倚不明显, 见图 9。
![]()
图 9 金龙胶囊联合放化疗对比单纯放化疗组治疗肝转移瘤的有效率漏斗图Figure 9 Comparison of effective rate between chemoradiotherapy group and chemoradiotherapy combined with Jinlong capsule group on liver metastases2.8 敏感度分析
对3组CD3、CD4和CD8的Meta分析所纳入的文献进行逐一排除, 并同时进行分析, 得到3项研究各自的敏感度分析结果, 发现排除蔡茂红[11]后, 其亚组异质性统计量I2分别从86%(χ2=14.76, P=0.0006)、38%(χ2=3.22, P=0.20)和87%(χ2=15.50, P=0.0004)下降至0(χ2=0.26, P=0.61)、0(χ2=0.09, P=0.76)和0(χ2=0.01, P=0.94), 其中CD8指标总效应经统计学分析, 其结果由差异无统计学意义(P=0.73)变为差异有统计学意义(P=0.003)。
2.9 生存期分析
纳入的8项研究仅有2项研究进行了长期随访, 因随访时间不一, 指标仅有一定参考意义, 有且只有2项研究, 故不作定量合成分析。其中孙保木等[7]长期随访两年, 最终对照组存活率4.7%, 实验组存活率23.8%, 差异有统计学意义。张晓前等[13]长期随访一年, 对照组生存率70%, 试验组生存率83%, 对照组有效患者无进展生存时间为7.8月, 试验组有效患者无进展生存期为11.3月。
3 讨论
肝转移瘤在临床上比较常见, 患者通常表现为肝脏进行性肿大并伴有肝区疼痛、消瘦、消化道症状。影像学表现肝内多个大小不等的结节, 无论从大小及数量上均快速增加。肿瘤压迫侵犯血管、胆管、神经, 造成门脉高压、黄疸及疼痛, 这与中医理论相契合。《素问五脏生成论》:"肝藏, 心行之, 人动则血运于诸经, 人静则血归于肝脏, ……肝主血海故也。"其病机演变过程为肿瘤毒邪在体内蕴藏, 入络客于血脉, 影响气、血、津、液的运行及输布, 此外肝气易郁结, 常易处于气郁血凝状态, 使脉络失于流畅, 导致毒滞络积聚, 引起络中气滞、血瘀或津凝等病理改变。
金龙胶囊以鲜守宫、鲜蕲蛇、鲜金钱白花蛇以2:1:1合理配比关系制成, 方中鲜守宫味咸, 性寒, 为君药, 入血分透筋达络、破瘀解毒散结、通经活络而止痛。鲜金钱白花蛇味咸, 性温、有毒, 为臣药, 具有通经络、止痉攻毒、破瘀散结止痛的作用, 辅助君药可加强破瘀散结、通络之功, 又能协同蕲蛇引药入肝经。鲜蕲蛇味甘咸, 性温, 入肝经, 为佐使药, 其性善走窜, 助君药滋阴破瘀散结, 加强臣药通络散结。全方配伍精当, 用二蛇之温制守宫寒, 用守宫之寒制二蛇之温, 相辅相成, 共奏抗肿瘤之功。大量临床研究证明金龙胶囊具有增强机体的细胞及体液免疫功能, 增强巨噬细胞、NK细胞活性, 增强LAK细胞、诱导干扰素、白介素肿瘤坏死因子、自然杀伤细胞的活性和淋巴因子的产生, 从而提高免疫功能达到抑制杀死肿瘤细胞的作用, 诱导肿瘤细胞凋亡, 提高疗效及生活质量, 减少患者的不良反应[15-21], 并对抑制肿瘤复发、自发转移、术后转移作用显著[22-23]。
从循证医学角度研究中医药临床疗效是中医药现代化重要组成部分, 本研究纳入文献仅8篇, 根据各项指标, 表明金龙胶囊能够有效提高肝转移瘤患者的临床疗效, 帮助免疫系统的恢复及减少对免疫系统的损伤和降低不良反应发生率, 据2项研究长期随访结果看, 存活率与无进展生存期试验组均占有优势。大多文献均发在中文杂志上, 存在根本上的发表偏倚。研究中纳入的8个研究质量普遍低, 均为中文文献, 均未交代具体的随机分组方法、分配隐藏及采取设盲的措施, 指标大同小异, 疗程周期长短不一致, 并且缺少长期性随访, 容易造成实施和测量偏倚, 所有的研究样本量普遍偏小, 8项研究中单个研究的总人数均较低, 8项研究的疗程基本在3月, 仅有孙保木与张晓前两项研究进行了长期随访, 但随访时间不一, 以上均降低了其检验效能。根据敏感度分析, 仔细审阅后发现基础治疗差异较大, 蔡茂红等未进行肝动脉栓塞, 可能为异质性产生的原因。受纳入试验数量和质量的限制, 仅以本系统评价为基础, 上述结论尚需开展更多大样本高质量的随机对照试验(RCT)进一步验证。将来应继续开展金龙胶囊联合放化疗治疗肝转移瘤的RCT, 进一步优化设计方案, 严格管理试验实施过程, 进行远期随访, 进一步评价金龙胶囊联合放化疗治疗肝转移瘤的疗效。本文受制于仅2项研究进行后期随访, 8项研究疗程3月, 疗程内与长期随访内无一例报道再发转移, 为后续研究关于金龙胶囊抑制肿瘤转移方面提供可能性。
综上所述, 金龙胶囊联合放化疗能够提高肝转移瘤患者的临床疗效、帮助免疫系统的恢复及减少对免疫系统的损伤和降低不良反应发生率。
Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：李笑宇：资料收集、文章撰写张 楠：文章修改狄 文：指导及审阅文章 -
表 1 近年来关于铂耐药性卵巢癌治疗的临床研究
Table 1 Recent clinical studies on the treatment of platinum-resistant ovarian cancer
Study Time Medication PFI Result McGuire WP, et al[16] 2009-2019 Olaratumab plus
liposomal doxorubicin
versus liposomal
doxorubicin alonePFI<12 months PFS: 18.1(8.7-27.0) versus 17.3(14.1-31.9)
OS: 72.3(52.4-86.7) versus 70.6(51.4-106.4)
ORR: 12.9%(6.6-22.1) versus 16.4%(9.2-26.2)
DOR: 39.1(26.1-56.1) versus 16.9(15.3-NA)Gaillard S, et al[17] 2015-2018 Lurbinectedin versus
pegylated liposomal
doxorubicin or
topotecanPFI 1-6 months PFS: 3.5(2.1-3.7) versus 3.6(2.7-3.8)
OS: 11.4(9.0-14.2) versus 10.9(9.3-12.5)
ORR: 14.5%(10.1-19.8) versus 12.7%(8.6-17.8)
DOR: 4.0(1.9-5.7) versus 3.7(3.6-7.2)McNeish IA, et al[18] 2010-2015 Saracatinib plus
paclitaxel versus
placebo plus
paclitaxelPFI<6 months PFS: 29(22-37) versus 34(23-46)
OS: 10.1(8.3-16.2) versus 12.3(11.0-14.4)
ORR: 29 versus 43
QoL: 66.9(1.89) versus 73.1(2.56)Liu JF, et al[19] 2011-2016 MM121 plus paclitaxel
versus paclitaxel alonePlatinum resistant
or refractoryPFS: 3.8(3.48-4.63) versus 3.7(2.56-5.52)
OS: 13.7(8.77-NA) versus 10.1(8.77-NA)Pujade-Lauraine E,
et al[20]2015-2019 Avelumab alone
versus avelumab plus
liposomal doxorubicin
versus liposomal
doxorubicin alonePFI<180 days OS: 11.8 (8.9-14.1) versus 15.7
(12.7-18.7) versus 13.1 (11.8-15.5)
PFS: 1.9 (1.8-1.9) versus 3.7
(3.3-5.1) versus 3.5 (2.1-4.0)
ORR: 3.7% (1.5-7.5) versus 13.3%
(8.8-19.0) versus 4.2% (1.8-8.1)
DOR: 9.2 (6.4-NA) versus 8.5
(6.1-NA) versus 13.1 (5.5-NA)
DCR: 33.0% (26.3-40.2) versus 57.4%
(50.0-64.6) versus 48.9% (41.6-56.3)Pujade-Lauraine E,
et al[21]2010-2014 Volasertib versus
chemotherapyPlatinum resistant
or refractoryDCR: 30.6% (18.0-43.2) versus 43.1% (29.5-56.7)
PFS: 13.1 (6.6-30.1) versus 20.6 (11.6-30.7)
OS: 60.1 (31.3-95.4) versus 68.6 (28.7-119.4)Pujade-Lauraine E,
et al[14]2009-2015 Chemotherapy versus
chemotherapy plus
bevacizumabPFI<6 months PFS: 3.4 (2.10-3.75) versus 6.8 (5.62-7.79)
ORR: 12.5% (7.1-17.9) versus 28.2% (20.8-35.6)
DOR: 5.4 (3.81-9.23) versus 9.4 (6.60-11.63)
OS: 9.4 (6.60-11.63) versus 16.6 (13.70-18.99)Lorusso D, et al[22] 2012-2016 Pertuzumab plus
chemotherapy versus
placebo plus
chemotherapyPlatinum resistant
or refractoryPFS: 4.3 (3.65-6.11) versus 2.7 (2.14-4.73)
ORR: 14.8% (7.0-26.2) versus 8.7% (3.3-18.0)
OS: 10.2 (6.67-15.24) versus 8.4 (6.14-11.99)Morre KN, et al[15] 2015-2020 Mirvetuximab
soravtansine
versus chemotherapyPFI<6 months PFS: 4.1 (3.75-4.53) versus 4.4 (2.83-5.59)
ORR: 22 (17.2-27.9) versus 12 (6.6-19.1)
OS: 15.6 (12.85-18.04) versus 13.9 (11.40-18.50)
CA125 react: 51 (44.1-58.3) versus 27 (17.6-37.8)
DOR: 5.7 (4.17-8.51) versus 7.3 (4.14-NA)
下载: 导出CSV
表 2 既往使用过其他治疗对复发时间及再次复发后治疗疗效的影响
Table 2 Effect of previous use of other treatments on time to recurrence and efficacy of subsequent treatment after recurrence
Study Previous treatment Treatment after recurrent Patient characteristic Result Cecere SC, et al[32] Olaparib after platinum-based chemotherapy Platinum-based chemotherapy PFI>12 months versus 6<PFI≤12 months versus PFI<6 months ORR: 22.2% versus 11.1% versus 9.5% Baert T, et al[33] Olaparib or no olaparib after platinum-based chemotherapy Platinum-based chemotherapy PARPi treatment before versus no PARPi treatment before DPR: 40% versus 9% Rose PG, et al[34] Olaparib or no olaparib after platinum-based chemotherapy Platinum-based chemotherapy PARPi treatment before versus no PARPi treatment before PFS: 8.0 versus 19.1 month (HR=4.01, 95%CI: 2.25-7.16, P<0.001) Frenel JS, et al[35] Olaparib or placebo after platinum-based chemotherapy Platinum- or non-platinum-based chemotherapy Placebo before versus olaparib before (All patients) TTSP: 12.1 versus 6.9 month (HR=2.17, 95%CI: 1.47-3.19)
(Patients with platinum-based chemotherapy) TTSP: 14.3 versus 7.0 (HR=2.89, 95%CI: 1.73-4.82)Himoto Y, et al[36] New adjuvant chemotherapy / PDS versus NACT-IDS NACT-IDS is associated with shorter time to recurrence (P=0.017, HR=1.57) Ekmann-Gade AW,
et al[37]New adjuvant chemotherapy / PDS versus NACT-IDS TFI: 372 days versus 497 days, P=0.042 Luo Y, et al[38] New adjuvant chemotherapy / PDS versus NACT-IDS Number of platinum-resistant diseases: 99/283 (35%) versus 29/58 (50%, OR=2.950, P=0.001) Petrillo M, et al[39] New adjuvant chemotherapy / PDS versus NACT-IDS PFI: 13 versus 21; P=0.014 Proportion of platinum-resistant diseases: 35.9% versus 5.0%; P=0.006 Note: TTSP: time to symptomatic progression.
下载: 导出CSV
-
[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. doi: 10.3322/caac.21834
[2] Stewart C, Ralyea C, Lockwood S. Ovarian Cancer: An Integrated Review[J]. Semin Oncol Nurs, 2019, 35(2): 151-156. doi: 10.1016/j.soncn.2019.02.001
[3] Wilson MK, Pujade-Lauraine E, Aoki D, et al. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: recurrent disease[J]. Ann Oncol, 2017, 28(4): 727-732. doi: 10.1093/annonc/mdw663
[4] Markman M, Rothman R, Hakes T, et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin[J]. J Clin Oncol, 1991, 9(3): 389-393. doi: 10.1200/JCO.1991.9.3.389
[5] Friedlander M, Trimble E, Tinker A, et al. Clinical trials in recurrent ovarian cancer[J]. Int J Gynecol Cancer, 2011, 21(4): 771-775. doi: 10.1097/IGC.0b013e31821bb8aa
[6] Armstrong DK, Alvarez RD, Bakkum-Gamez JN, et al. Ovarian Cancer, Version 2. 2020, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2021, 19(2): 191-226.
[7] Havasi A, Cainap SS, Havasi AT, et al. Ovarian Cancer-Insights into Platinum Resistance and Overcoming It[J]. Medicina (Kaunas), 2023, 59(3): 544. doi: 10.3390/medicina59030544
[8] Davis A, Tinker AV, Friedlander M. "Platinum resistant" ovarian cancer: what is it, who to treat and how to measure benefit?[J]. Gynecol Oncol, 2014, 133(3): 624-631. doi: 10.1016/j.ygyno.2014.02.038
[9] da Costa AABA, Dos Santos ES, Cotrim DP, et al. Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis[J]. BMC Cancer, 2019, 19(1): 1194. doi: 10.1186/s12885-019-6382-x
[10] Baert T, Ferrero A, Sehouli J, et al. The systemic treatment of recurrent ovarian cancer revisited[J]. Ann Oncol, 2021, 32(6): 710-725. doi: 10.1016/j.annonc.2021.02.015
[11] St Laurent J, Liu JF. Treatment Approaches for Platinum-Resistant Ovarian Cancer[J]. J Clin Oncol, 2024, 42(2): 127-133. doi: 10.1200/JCO.23.01771
[12] Pejovic T, Fitch K, Mills G. Ovarian cancer recurrence: “is the definition of platinum resistance modified by PARP inhibitors and other intervening treatments?”[J]. Cancer Drug Resist, 2022, 5(2): 451-458. doi: 10.20517/cdr.2021.138
[13] Richardson DL, Eskander RN, O'Malley DM. Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum Resistance: A Narrative Review[J]. JAMA Oncol, 2023, 9(6): 851-859.
[14] Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase Ⅲ trial[J]. J Clin Oncol, 2014, 32(13): 1302-1308.
[15] Moore KN, Vergote I, Oaknin A, et al. FORWARD Ⅰ: a Phase Ⅲ study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer[J]. Future Oncol, 2018, 14(17): 1669-1678. doi: 10.2217/fon-2017-0646
[16] McGuire WP, Penson RT, Gore M, et al. Randomized phase Ⅱ study of the PDGFRα antibody olaratumab plus liposomal doxorubicin versus liposomal doxorubicin alone in patients with platinum-refractory or platinum-resistant advanced ovarian cancer[J]. BMC Cancer, 2018, 18(1): 1292. doi: 10.1186/s12885-018-5198-4
[17] Gaillard S, Oaknin A, Ray-Coquard I, et al. Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL)[J]. Gynecol Oncol, 2021, 163(2): 237-245. doi: 10.1016/j.ygyno.2021.08.032
[18] McNeish IA, Ledermann JA, Webber L, et al. A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer[J]. Ann Oncol, 2014, 25(10): 1988-1995. doi: 10.1093/annonc/mdu363
[19] Liu JF, Ray-Coquard I, Selle F, et al. Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer[J]. J Clin Oncol, 2016, 34(36): 4345-4353. doi: 10.1200/JCO.2016.67.1891
[20] Pujade-Lauraine E, Fujiwara K, Dychter SS, et al. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase Ⅲ study design[J]. Future Oncol, 2018, 14(21): 2103-2113. doi: 10.2217/fon-2018-0070
[21] Pujade-Lauraine E, Selle F, Weber B, et al. Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase Ⅱ Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study[J]. J Clin Oncol, 2016, 34(7): 706-713. doi: 10.1200/JCO.2015.62.1474
[22] Lorusso D, Hilpert F, González Martin A, et al. Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer[J]. Int J Gynecol Cancer, 2019, 29(7): 1141-1147. doi: 10.1136/ijgc-2019-000370
[23] Champer M, Huang Y, Hou JY, et al. Adherence to treatment recommendations and outcomes for women with ovarian cancer at first recurrence[J]. Gynecol Oncol, 2018, 148(1): 19-27. doi: 10.1016/j.ygyno.2017.11.008
[24] Lindemann K, Gao B, Mapagu C, et al. Response rates to second-line platinum-based therapy in ovarian cancer patients challenge the clinical definition of platinum resistance[J]. Gynecol Oncol, 2018, 150(2): 239-246. doi: 10.1016/j.ygyno.2018.05.020
[25] Tatsuki S, Shoji T, Abe M, et al. Efficacy and Safety of Platinum Rechallenge in Patients With Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer: A Multicenter Retrospective Study[J]. Anticancer Res, 2022, 42(9): 4603-4610. doi: 10.21873/anticanres.15964
[26] Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer[J]. N Engl J Med, 2019, 381(25): 2416-2428. doi: 10.1056/NEJMoa1911361
[27] DiSilvestro P, Banerjee S, Colombo N, et al. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial[J]. J Clin Oncol, 2023, 41(3): 609-617. doi: 10.1200/JCO.22.01549
[28] McMullen M, Karakasis K, Madariaga A, et al. Overcoming platinum and PARP-inhibitor resistance in ovarian cancer[J]. Cancers (Basel), 2020, 12(6): 1607. doi: 10.3390/cancers12061607
[29] Park J, Kim SI, Jeong SY, et al. Second-line olaparib maintenance therapy is associated with poor response to subsequent chemotherapy in BRCA1/2-mutated epithelial ovarian cancer: A multicentre retrospective study[J]. Gynecol Oncol, 2022, 165(1): 97-104. doi: 10.1016/j.ygyno.2022.02.002
[30] Liu J, Jiao X, Gao Q. Neoadjuvant chemotherapy-related platinum resistance in ovarian cancer[J]. Drug Discov Today, 2020, 25(7): 1232-1238. doi: 10.1016/j.drudis.2020.04.015
[31] Lim MC, Song YJ, Seo SS, et al. Residual cancer stem cells after interval cytoreductive surgery following neoadjuvant chemotherapy could result in poor treatment outcomes for ovarian cancer[J]. Onkologie, 2010, 33(6): 324-330. doi: 10.1159/000313823
[32] Cecere SC, Giannone G, Salutari V, et al. Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome[J]. Gynecol Oncol, 2020, 156(1): 38-44. doi: 10.1016/j.ygyno.2019.10.023
[33] Baert T, Ataseven B, Bommert M, et al. 828P Expected observed response to platinum-based chemotherapy after poly (ADP-ribose) polymerase inhibitor treatment for relapsed ovarian cancer[J]. Ann Oncol, 2020, 31(Suppl 4): S624.
[34] Rose PG, Yao M, Chambers LM, et al. PARP inhibitors decrease response to subsequent platinum-based chemotherapy in patients with BRCA mutated ovarian cancer[J]. Anticancer Drugs, 2021, 32(10): 1086-1092. doi: 10.1097/CAD.0000000000001219
[35] Frenel JS, Kim JW, Aryal N, et al. Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial[J]. Ann Oncol, 2022, 33(10): 1021-1028. doi: 10.1016/j.annonc.2022.06.011
[36] Himoto Y, Cybulska P, Shitano F, et al. Does the method of primary treatment affect the pattern of first recurrence in high-grade serous ovarian cancer?[J]. Gynecol Oncol, 2019, 155(2): 192-200. doi: 10.1016/j.ygyno.2019.08.011
[37] Ekmann-Gade AW, Hogdall CK, Engelholm SA, et al. Neoadjuvant Chemotherapy Reduces the Treatment-free Interval After First-line Treatment in Patients With Advanced Ovarian Cancer[J]. Anticancer Res, 2020, 40(5): 2765-2770. doi: 10.21873/anticanres.14248
[38] Luo Y, Lee M, Kim HS, et al. Effect of neoadjuvant chemotherapy on platinum resistance in stage ⅢC and Ⅳ epithelial ovarian cancer[J]. Medicine (Baltimore), 2016, 95(36): e4797. doi: 10.1097/MD.0000000000004797
[39] Petrillo M, Ferrandina G, Fagotti A, et al. Timing and pattern of recurrence in ovarian cancer patients with high tumor dissemination treated with primary debulking surgery versus neoadjuvant chemotherapy[J]. Ann Surg Oncol, 2013, 20(12): 3955-3960. doi: 10.1245/s10434-013-3091-6
[40] Colombo N, Sessa C, du Bois A, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease[J]. Ann Oncol, 2019, 30(5): 672-705. doi: 10.1093/annonc/mdz062
[41] Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers[J]. JAMA, 2017, 317(23): 2402-2416. doi: 10.1001/jama.2017.7112
[42] Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers[J]. Nat Rev Cancer, 2004, 4(10): 814-819. doi: 10.1038/nrc1457
[43] Tan DS, Rothermundt C, Thomas K, et al. “BRCAness”syndrome in ovarian cancer: a case–control study describing the clinical features and outcome of patients with epithelial ovarian cancer associated with BRCA1 and BRCA2 mutations[J]. J Clin Oncol, 2008, 26(34): 5530-5536. doi: 10.1200/JCO.2008.16.1703
[44] Bu H, Chen J, Li Q, et al. BRCA mutation frequency and clinical features of ovarian cancer patients: A report from a Chinese study group[J]. J Obstet Gynaecol Res, 2019, 45(11): 2267-2274. doi: 10.1111/jog.14090
[45] Alsop K, Fereday S, Meldrum C, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group[J]. J Clin Oncol, 2012, 30(21): 2654-2663. doi: 10.1200/JCO.2011.39.8545
[46] Gu P, Pan LL, Wu SQ, et al. CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma: a systematic review and meta-analysis[J]. Eur J Radiol, 2009, 71(1): 164-174. doi: 10.1016/j.ejrad.2008.02.019
[47] Hall M, Rustin G. Recurrent ovarian cancer: when and how to treat[J]. Curr Oncol Rep, 2011, 13(6): 459-471. doi: 10.1007/s11912-011-0199-3
[48] Rustin GJ, Nelstrop AE, Tuxen MK, et al. Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group Study[J]. Ann Oncol, 1996, 7(4): 361-364. doi: 10.1093/oxfordjournals.annonc.a010602
[49] Wilder JL, Pavlik E, Straughn JM, et al. Clinical implications of a rising serum CA-125 within the normal range in patients with epithelial ovarian cancer: a preliminary investigation[J]. Gynecol Oncol, 2003, 89(2): 233-235. doi: 10.1016/S0090-8258(03)00051-9
[50] Lee CK, Simes RJ, Brown C, et al. A prognostic nomogram to predict overall survival in patients with platinum-sensitive recurrent ovarian cancer[J]. Ann Oncol, 2013, 24(4): 937-943. doi: 10.1093/annonc/mds538
[51] Atallah GA, Kampan NC, Chew KT, et al. Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers[J]. Int J Mol Sci, 2023, 24(3): 1973. doi: 10.3390/ijms24031973
[52] Pylväs-Eerola M, Liakka A, Puistola U, et al. Cancer Stem Cell Properties as Factors Predictive of Chemoresistance in Neoadjuvantly-treated Patients with Ovarian Cancer[J]. Anticancer Res, 2016, 36(7): 3425-3431.
[53] Uno K, Yoshikawa N, Tazaki A, et al. Significance of platinum distribution to predict platinum resistance in ovarian cancer after platinum treatment in neoadjuvant chemotherapy[J]. Sci Rep, 2022, 12(1): 4513. doi: 10.1038/s41598-022-08503-7
[54] Patch AM, Christie EL, Etemadmoghadam D, et al. Whole-genome characterization of chemoresistant ovarian cancer[J]. Nature, 2015, 521(7553): 489-494. doi: 10.1038/nature14410
-
期刊类型引用(5)
1. 王静，贾建伟，苗静，郭丽颖. 肝动脉化疗栓塞联合金龙胶囊治疗血瘀郁结证中晚期肝癌疗效及对机体免疫功能的影响. 山西医药杂志. 2022(04): 367-370 . 
百度学术
2. 韩东，王珊，王乐，龚伟玲，彭修娟，李波，刘峰. 基于中国知网数据库(1978-2020年)中药鲜药鲜用研究的知识图谱及数据可视化分析. 世界科学技术-中医药现代化. 2022(11): 4140-4148 . 百度学术
3. 邝玉慧，徐方飚，赵哲，梁家琦，陈欣菊. 复方斑蝥胶囊联合不同放化疗方案治疗原发性肝癌有效性与安全性的Meta分析及试验序贯分析. 中国药房. 2021(08): 996-1003 . 百度学术
4. 王肖，张瑾莉，王立新. 某院2018～2020年原发性肝癌患者中成药用药情况分析. 中国处方药. 2021(09): 66-68 . 百度学术
5. 曾春生，余瑛，徐青云，王小毛，廖振蓉. 金龙胶囊在宫颈癌术后调强放疗复发转移中的应用效果. 中国当代医药. 2021(28): 148-151 . 百度学术
其他类型引用(0)
计量
- 文章访问数: 1428
- HTML全文浏览量: 2853
- PDF下载量: 824
- 被引次数: 5
