《铂类药物晚期乳腺癌应用专家共识（2020版）》解读

铂类药物是乳腺癌化疗中的常用药物，通过规范化疗方案和合理优化治疗策略，可延长晚期患者的生存时间，改善预后。中国医师协会肿瘤医师分会乳腺癌学组为指导铂类药物在晚期乳腺癌中的临床应用，制定了《铂类药物晚期乳腺癌应用专家共识（2020版）》。本文针对该共识进行解读，为晚期乳腺癌个体化诊疗提供科学依据。      

长春瑞滨或吉西他滨联合顺铂治疗耐药的晚期乳腺癌

乳腺癌是妇女常见的恶性肿瘤,含蒽环类和紫杉类药物的化疗方案广泛应用于乳腺癌的一线治疗,但对上述药物治疗后出现的复发、转移尚无公认的标准替代方案。如何治疗该类药物化疗失败的晚期乳腺癌患者成为临床医师面临的难题。从2002年2月～2007年3月,我们应用国产长春瑞滨与吉西他滨分别联合顺铂方案,治疗既往经蒽环类和／或紫杉类化疗后转移的乳腺癌患者66例,观察其近期疗效及不良反应,现报告如下。     

铂类药物在头颈部鳞癌治疗中的选择与应用

以铂类药物为基础的化疗成为晚期头颈部鳞癌（head and neck squamous cell carcinoma，HNSCC）综合治疗中不可缺少的部分。化疗可与放疗同步用于局部晚期HNSCC的根治性治疗，或用于具有高危因素的HNSCC术后辅助治疗，也可用于诱导化疗（新辅助化疗）或者放疗后的辅助化疗。同期放化疗在局部晚期HNSCC的治疗中尤其重要。几种常用的铂类药物在HNSCC的治疗中各有优势。本文简述铂类药物的药理作用及机制，比较铂类药物在HNSCC的疗效与毒性，并分析不同给药方式（单药或多药联合，每周或每3周）与给药剂量所带来的疗效与毒性差异，希望能对医师合理使用铂类药物治疗HNSCC有所裨益。     

多西紫杉醇联合顺铂治疗晚期乳腺癌临床观察

目的:观察多西紫杉醇联合顺铂方案治疗化疗后复发转移晚期乳腺癌的临床疗效和不良反应.方法:晚期乳腺癌32例其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗14例.用多西紫杉醇70mg/m2,第1天静滴,顺铂25mg/m2,第1-3天静滴,21天为1周期,2周期后评价疗效.结果:32例中CR 3例,PR 14例,总有效率为53.1%,中位疾病进展时间9个月,中位生存期17.8个月.主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受.结论:多西紫杉醇顺铂联合治疗化疗后复发转移的晚期乳腺癌疗效确切,副作用较轻可耐受.     

泰索帝联合顺铂治疗蒽环类药物耐药的晚期乳腺癌的临床研究

目的研究泰索帝联合顺铂治疗蒽环类药物耐药的晚期乳腺癌的疗效和安全性。方法28例蒽环类药物治疗失败的晚期乳腺癌患者均接受泰索帝联合顺铂方案治疗泰索帝75mg/m2静滴,第1天;顺铂80mg/m2静滴,第1天或分3天给予;每3周重复,完成3个周期化疗后评价疗效,有效病例4周后确认。结果28例患者均可评价疗效,CR3例,PR13例,SD11例,PD1例,总有效率(CR PR)57.1%(16/28)。主要不良反应为骨髓抑制。结论泰索帝联合顺铂是治疗蒽环类药物耐药的晚期乳腺癌的有效化疗方案,不良反应能够耐受。     

盖诺加顺铂治疗对葸环类耐药乳腺癌的临床观察

含蒽环类药物方案(如CAF)已被公认为是治疗晚期乳腺癌的最佳方案，但临床仍有20％～30％的患产生耐药性和心脏毒性，临床上仍需寻找高效、低毒且价格相对适宜的二线化疗方案。我们于1999年1月～2001年12月，采用盖诺加顺铂治疗对蒽环类药物耐药的44例晚期乳腺癌患，现将研究结果报告如下。     

紫杉醇对复发转移性乳腺癌的临床疗效观察

目的 观察紫杉醇对复发、转移性、抗铂类药物的乳腺癌的临床疗效。方法 17例复发、转移性、抗铂类药物的乳腺癌病人临床应用。结果 17例患者中,可评价疗效者14例,完全缓解43％,总分缓解57％,总有效率100％。结论 紫杉醇是一种安全、有效的药物,对晚期复发转移性抗铂类药物的乳腺癌患者应当给予紫杉醇治疗。     

盖诺加顺铂治疗对蒽环类耐药乳腺癌的临床观察

含蒽环类药物方案 (如CAF)已被公认为是治疗晚期乳腺癌的最佳方案 ,但临床仍有 2 0 %～ 30 %的患者产生耐药性和心脏毒性 ,临床上仍需寻找高效、低毒且价格相对适宜的二线化疗方案。我们于 1999年 1月～ 2 0 0 1年 12月 ,采用盖诺加顺铂治疗对蒽环类药物耐药的 4 4例晚期乳腺癌患者 ,现将研究结果报告如下。一、材料与方法1.一般资料 :经病理确诊的晚期乳腺癌患者 4 4例 ,均为女性。年龄 2 2～ 6 8岁 ,中位年龄 4 9岁。 31例行改良根除术或根除术 ,其中 10例行辅助化疗 ,2 1例行辅助化疗 放疗 ;13例未行手术治疗。 4 4例患者中 ,以含蒽环…     

吉西他滨联合顺铂治疗耐药的转移性乳腺癌的临床观察

随着蒽环类和紫杉类药物在乳腺癌治疗中的应用,乳腺癌的治疗有了长足的进步,如何治疗该类药物化疗后失败的晚期乳腺癌患者成为临床医师面临的难题。吉西他滨(GEM,健择)不论单药或联合用药对乳腺癌都有较高的疗效[1],另有报道健择对紫杉醇耐药的乳腺癌有一定效果[2],为此自2000年3月以来,我们应用健择联合顺铂(DDP)治疗既往经蒽环类和/或紫杉类化疗后转移的晚期乳腺癌患者24例,收到较好的疗效,现报告如下:1资料与方法1.1一般资料24例患者,年龄为31~65岁,中位年龄41岁,KPS≥60分。均经手术切除或穿刺活检后病理证实为乳腺癌,并通过免疫组…     

ERCC2 rs1799793多态性与三阴性乳腺癌铂类化疗疗效的关系

背景与目的:DNA修复基因的多态性可以影响DNA损伤修复能力,从而影响患者的化疗疗效。切除修复交叉互补基因2(excision repair cross-complementing group 2,ERCC2)参与核苷酸切除修复和基因转录,在DNA损伤修复中起重要作用。本研究旨在初步探讨ERCC2单核苷酸多态性与三阴性乳腺癌铂类药物化疗疗效的关系。方法:全组患者中位年龄46岁,中位化疗周期数为4个周期。60例接受铂类药物化疗的晚期或局部晚期三阴性乳腺癌患者,收集其临床病理资料和随访信息,采用高通量MassARRAY时间飞行质谱生物芯片系统分析入组患者ERCC2基因候选位点的单核苷酸多态性,观察比较不同基因型与化疗疗效之间的关系。结果:接受含铂方案治疗的总体有效率为66.7%。60例中53例获得ERCC2 rs1799793位点检测结果,ERCC2rs1799793位点等位基因型有GG、GA 2种,频率分别为81.1%、18.9%。GG基因型患者化疗有效30例,无效13例;GA基因型患者化疗有效3例,无效7例。两组的化疗有效率分别为69.8%和30.0%,疗效差异有统计学意义(P=0.030),携带GG基因型的患者化疗敏感性高于携带GA基因型患者。结论:ERCC2基因rs1799793多态性与三阴性乳腺癌患者接受铂类药物化疗的临床疗效有关。     

BRCA1/2突变和同源重组修复缺陷(HRD)检测在乳腺癌中的临床研究进展

乳腺癌已成为发病率最高的癌症。DNA修复缺陷是乳腺癌最重要的特征之一。先前的研究表明,乳腺癌易感基因1/2(breast cancer susceptibility gene 1/2,BRCA1/2)突变是预测乳腺癌同源重组修复缺陷(homologous recombination deficiency, HRD)最主要的生物标志物,能识别铂类药物和多腺苷二磷酸核糖聚合酶(poly ADP ribose polymerase, PARP)抑制剂治疗的获益人群。美国食品药品监督管理局(FDA)已批准Olaparib和Talazoparib两种PARP抑制剂,用于BRCA1/2突变的早期和晚期乳腺癌的辅助治疗。但中国尚未获批。现有研究表明,一部分非BRCA1/2突变的乳腺癌患者也具有HRD特征,可以从铂类药物或PARP抑制剂中获益。本综述总结了涉及到BRCA1/2突变、同源重组修复(homologous recombination repair, HRR)基因突变和HRD状态检测的临床研究。阐明了各种检测方法在识别乳腺癌患者HRD状态和预测疗效方面的价值,并提出应尽快开发用于中国乳腺癌HR...     

胚系BRCA基因突变乳腺癌的临床诊治进展

BRCA基因是最常见的乳腺癌易感基因,胚系BRCA突变患者罹患乳腺癌的风险显著增加.随着对BRCA基因的深入研究以及聚ADP-核糖聚合酶(poly ADP-ribose polymerase,PARP)抑制剂的出现,BRCA突变已成为乳腺癌治疗的新靶点.在BRCA突变乳腺癌的治疗中,PARP抑制剂和铂类为两大主要药物选...     

Rationale for the use of gemcitabine in breast cancer (Review)

Many active cytotoxic drugs and several regimens exist for breast cancer therapy. However, these conventional treatments have not changed the outcome of patients with locally advanced and metastatic disease. As a consequence, the dynamic balance between chemotherapy-induced side effects and benefits attributable to relief of cancer-related symptoms must be carefully considered in this setting. Gemcitabine is a pyrimidine nucleoside antimetabolite that has shown activity in a variety of solid tumors, a good toxicity profile, and non-overlapping toxicity with other chemotherapeutic drugs. As a single agent, gemcitabine yields response rates ranging from 14 to 37% as first-line treatment for advanced breast cancer and 12-30% as salvage therapy for patients previously treated with anthracycline and/or taxane treatment. Combined with vinorelbine, platinum, anthracyclines, and taxanes as doublets or triplets, response rates of 50 to 80% have been reported in phase II clinical studies. Gemcitabine in combination with anthracyclines and taxanes has been evaluated in the neoadjuvant setting in patients with early-stage breast cancer with interesting clinical and pathological response rates. Preliminary results of gemcitabine in combination with the biologic agent, trastuzumab, are encouraging. Phase III trials of gemcitabine combinations compared to standard regimens are ongoing with the aim to assess the independent contribution of gemcitabine.     

New drugs in gynecologic cancer

Opinion statement The implementation of new drug treatments has improved the prognosis for advanced cancers of the cervix, uterus, and ovary. Platinum analogs are the most effective drugs in the treatment of ovarian cancer. Other drugs, such as oxaliplatin, have been proposed as a rational treatment of platinum refractory ovarian cancer. Epothilones are also being studied in clinical trials, as are histone deacetylase inhibitors. Several promising agents may soon receive Food and Drug Administration approval.     

Current and future potential roles of the platinum drugs in the treatment of ovarian cancer

The discovery of cisplatin more than two decades ago was the most importanttherapeutic advance in the treatment of ovarian cancer. Today, cisplatin orcarboplatin in combination with paclitaxel is the most commonly usedfirst-line treatment for patients with advanced ovarian cancer.Although platinum drugs remain a critical component of chemotherapy in thistype of cancer, cumulative toxicities can limit their use. These toxicitiesinclude nephrotoxicity, neurotoxicity and ototoxicity with cisplatin andmyelosuppression with carboplatin. Although these adverse events can often bemanaged, the interventions themselves can complicate and add to the costs oftreatment. Importantly, acquired resistance to traditional platinum drugsoften develops in patients with ovarian cancer and can limit the usefulnessof these drugs.Research into new platinum drugs has focused on identifying compounds withimproved tolerability profiles and, importantly, those which can circumventmechanisms of platinum resistance. New platinum drugs currently underdevelopment that are showing promise in ovarian cancer include oxaliplatin,nedaplatin, satraplatin, BBR3464 and ZD0473. If the encouraging invitro activity shown by new compounds, such as ZD0473 and BBR3464,translates into efficacy in the clinic, they may offer an extended spectrumof activity which includes patients with ovarian cancer resistant to theclassical platinum drugs.     

激素受体阳性晚期乳腺癌内分泌治疗选择

激素受体阳性乳腺癌占所有乳腺癌的70%。内分泌治疗是这个亚型乳腺癌的主要治疗手段,最常见药物有他莫昔芬和芳香酶抑制剂如阿拉曲唑、来曲唑和依西美坦。全文重点总结新型内分泌治疗药物,如雌激素受体降解剂(Fulvestrant),以及新的靶向药物如mTOR抑制剂(Everolimus)、CDK4/6抑制剂(Palbociclib、Ribociclib和Abemaciclib)和PI3K抑制剂(Alpelisib、Buparlisib和Pictilisib)等。新的靶向药物联合内分泌治疗已经改变了临床实践,延长激素受体阳性晚期乳腺癌患者的生存期。     

Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease

For women with advanced ovarian cancer, rates of response to first-line chemotherapy are high but most patients have relapses and become candidates for further chemotherapy. Chemotherapy for recurrence can palliate symptoms, and there is some evidence that it can also improve survival in this clinical situation. Patients who relapse quickly after first-line therapy should not be given the same drugs as were used initially. However, for patients who have longer intervals from treatment to relapse, the rates of response to a rechallenge with platinum are clinically significant. Several cytotoxic drugs have shown activity in patients whose disease has relapsed after therapy with platinum and a taxane; these drugs include topotecan, etoposide, pegylated liposomal doxorubicin, epirubicin, gemcitabine, altretamine, oxali platin, and vinorelbine. Recurrent ovarian cancer is also an important setting in which to test investigational agents with promising activity, such as new platinum compounds, new taxanes, and other cytotoxic agents, as well as non-cytotoxic compounds with novel mechanisms of action.     

第３代铂类药物洛铂的研究新进展

洛铂是第３代新的铂类抗肿瘤药物,已获国家ＳＦＤＡ批准上市用于治疗晚期乳腺癌、小细胞肺癌和慢性粒细胞白血病。为了进一步提高临床医师对于洛铂的认识和重视,本文就近年来基础和临床研究新的重要文献作一综述。     

Novel Cytotoxic Agents in the Treatment of Metastatic Breast Cancer

Breast cancer is the most common cancer affecting women worldwide, comprising approximately 20% of all cancers. Although many advances in the treatment of this disease have been made and mortality of early breast cancer improved over the past three decades, metastatic breast cancer (MBC) remains an incurable disease. Cytotoxic chemotherapy continues to play a major role in the treatment of MBC and has been recently combined with biologic agents such as monoclonal antibodies or kinase inhibitors. Over the past decade, several novel cytotoxic chemotherapies have been evaluated in clinical trials. Encouraging results have been observed with novel anti-microtubule agents, with recent US Food and Drug Administration approval of eribulin in 2010. Other novel cytotoxic agents currently under clinical development include novel anti-microtubule drugs, platinum compounds, and anti-angiogenic agents combined with chemotherapy. Here, we review all the major novel cytotoxic agents that have undergone clinical study over the past 5 years for the treatment of MBC.