晚期结直肠癌内科治疗进展

晚期转移性结直肠癌的5年生存率低于10％。5-FU／LV方案治疗的中位生存期大约12个月。最近化疗方案的更新延长了患者的中位生存期。研究发现奥沙利铂、伊立替康联合5-FU／LV或者卡培他滨等化疗方案使中位生存期延长到20个月。奥沙利铂，伊立替康联合5-FU／LV比传统的单药5-FU／LV使生活质量改善时间延长。目前转移性结直肠癌标准的一线治疗方案为FOLFOX和FOLFIRI。正在进行的研究关注新的分子靶向药物（molecular targeted therapy）联合化疗治疗转移性结直肠癌，且部分试验取得了较好的疗效。本文将对5-FU、新一代化疗药物以及分子靶向药物在转移性结肠癌治疗的演进及新进展作一综述。     

BRAF基因突变转移性结直肠癌治疗进展

BRAF基因突变结直肠癌是一种具有独特临床病理特征的亚型,BRAF突变以BRAFV600E突变最为常见。BRAFV600E突变结直肠癌的疗效和预后较差,晚期一线可选择化疗联合抗血管生成药物的治疗策略,后线治疗采用BRAF抑制剂联合表皮生长因子受体抑制剂方案可为患者带来生存获益。目前BRAFV600E突变转移性结直肠癌的治疗探索包括阻断各种细胞信号传导通路的靶向药物联合以及靶向治疗与免疫治疗联合等治疗策略。文章就BRAF突变转移性结直肠癌的分子生物学特点、临床病理特征以及BRAFV600E突变转移性结直肠癌的治疗进展进行综述。     

2023年ASCO转移性结直肠癌免疫治疗和靶向治疗进展

结直肠癌是最常见的恶性肿瘤之一,全球发病率位居第三。2023年6月,第59届美国临床肿瘤学会年会在美国召开。会议公布了多项结直肠癌治疗的研究成果,为临床治疗指引方向。本文就本届会议上转移性结直肠癌免疫和靶向治疗领域的重要研究进展作整理报道。     

晚期结直肠癌分子靶向治疗的研究进展

结直肠癌是人类最常见的恶性肿瘤之一,分子靶向治疗药物近年来在对晚期结直肠癌患者的综合治疗中发挥了重要作用,因此结直肠癌的靶向治疗已经成为临床研究的热点。目前晚期结直肠癌靶向治疗的代表药物主要有两大类,一类是以血管内皮生长因子为作用靶点的贝伐单抗(bevacizumab)等药物,通过抑制肿瘤血管的新生来抑制肿瘤的生长;另一类是以表皮生长因子受体为作用靶点的西妥昔单抗(cetuximab)及帕尼单抗(panitumumab)等药物,通过与肿瘤细胞表面的表皮生长因子受体特异性结合来竞争性阻断其与其他配体的结合来达到抑制肿瘤生长的目的。两类分子靶向治疗药物的作用靶点各不相同,因此在临床治疗过程中所产生的疗效也不同,且分子靶向治疗药物在临床上的应用尚存在许多问题有待进一步阐明。     

晚期结直肠癌三线及三线以上治疗的研究进展

结直肠癌是消化道最常见恶性肿瘤之一,大多数结直肠癌患者就诊时已属中晚期,失去手术机会.化疗及分子靶向治疗为结直肠癌的有效治疗手段.目前,晚期结直肠癌的三线治疗尚无标准方案.全文对晚期结直肠癌的三线及三线以上治疗相关的临床研究进行了简要分析.     

转移性结直肠癌维持治疗研究进展

结直肠癌是最常见的恶性肿瘤之一。近年来,奥沙利铂、5-FU类制剂、伊立替康、VEGF抗体、EGFR抑制剂等药物的使用延长了晚期结直肠癌患者的5年生存率,显著改善患者的生活质量。维持治疗是指对一线治疗后获益的患者,停用某些毒副反应较大的药物,保留低毒性药物继续治疗的一种治疗模式。因此,一些临床研究评估了上述药物在转移性结直肠癌患者一线治疗获益后的维持治疗的疗效及安全性。本文就转移性结直肠癌维持治疗方案的临床研究作一综述,全面地了解转移性结直肠癌维持治疗的相关进展。     

HER2阳性结直肠癌研究进展

表皮生长因子受体2（HER2）是肿瘤发生、发展过程中的癌基因,在7%的结直肠癌患者中表达,与表皮生长因子受体单克隆抗体的耐药相关。随着CRC治疗困境的出现,以及靶向HER2为乳腺癌、胃癌患者带来生存获益,HER2在CRC中的意义及抗HER2治疗的预后价值被广泛关注,围绕HER2阳性CRC的临床研究亦不断开展。目前,CRC中HER2阳性的诊断标准已逐渐统一,HER2靶向治疗如单克隆抗体、酪氨酸激酶抑制剂、抗体-药物耦联物及HER2相关免疫治疗的单独或联合治疗策略在HER2阳性CRC中显示出较好的疗效,能为患者带来生存获益,本文就此方面的研究进展作一综述。     

晚期转移性结直肠癌内科治疗进展

结直肠癌的发病率在世界各国尤其是发达国家中明显上升,近20年来在我国尤其是在大城市,结直肠癌的发病率已占消化道癌的第二位。2000年,世界范围内,结直肠癌新发病例940000,其中死亡254000例。目前,由于结直肠癌的诊断手段、手术技术及支持治疗的进步,Ⅰ、Ⅱ、Ⅲ期结直肠癌患者的5年生存率明显升高,但对于已经出现转移的结直肠癌患者,5年生存率仍然很低。复发转移性结直肠癌的主要治疗手段是化疗,1996年后伊立替康、奥沙利铂与卡陪他滨相继问世,新一代药物可使中位生存时间延长到20个月,单克隆抗体与化疗联合又使中位生存时间延长到24个月左右,这在晚期实体癌的化疗史上是了不起的进步。     

RAS基因突变型转移性结直肠癌的治疗研究进展

结直肠癌是常见的消化道肿瘤之一,部分结直肠癌患者确诊时已发生转移,以化疗为主的综合治疗是转移性结直肠癌(mCRC)患者的主要治疗策略。近10余年来,靶向治疗的出现改善了mCRC患者的预后。目前临床用于m CRC的靶向治疗药物主要包括以表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)为靶点的药物。而前期诸多研究已经证实了有大鼠肉瘤病毒(RAS)基因突变的mCRC患者对抗EGFR治疗无效。因此,RAS基因突变型mCRC的治疗存在局限性。本文针对RAS基因突变型mCRC的治疗进展进行综述。     

Ongoing and future directions in the management of metastatic colorectal cancer: Update on clinical trials

Metastatic colorectal cancer (mCRC) continues to show poor outcomes, with many patients exhausting effective standard-of-care therapy. To explore the current landscape of clinical trials for mCRC, we reviewed over 600 clinical trials that are currently ongoing for mCRC patients. Immunotherapeutic agents form approximately 39% (includes monoclonal antibodies, viruses, vaccines, and immunomodulators) of all agents and targeted therapy forms 45% (tyrosine kinase inhibitors, epigenetic modulators, and others) of all agents being investigated for mCRC.     

Systemic treatment for metastatic colorectal cancer in the era of precision medicine

The treatment of metastatic colorectal cancer has evolved over the last two decades with the FDA approval of several cytotoxic, biological, and targeted agents. In this paper, we review the impact of sidedness, RAS, BRAF, HER-2, and other immune biomarkers on metastatic colorectal cancer treatment selection and sequencing in both the palliative and curative intent settings.     

The changing face of treatment for metastatic colorectal cancer

Introduction: Since late 1990’s therapy of metastatic colorectal cancer (mCRC) patients has changed considerable, and the combination of doublet or triplet chemotherapy and a targeted agent are now routinely used. With the introduction of more intensified regimens, it has become even more important to identify patients that will benefit from and can tolerate therapy. Furthermore, the increasing understanding of the biology of mCRC has led to the discovery of new potential targets. Therefore, therapy of patients with mCRC has undergone considerable change from ‘one strategy fits all’ towards a more personalized therapy.

Areas covered: We present an overview of the recent literature on approved systemic treatment of mCRC however with focus on how the treatment strategy has changed based on clinical and molecular parameters that presently are used routinely in the clinical situation.

Expert commentary: The face of treatment of mCRC has changed from ‘one strategy fits all’ to a personalized approach in which both clinical, molecular parameters and the aim of therapy have to be taking into account when planning the optimal treatment strategy for the individual mCRC patient.     

Targeted therapy for colorectal cancer metastases: A review of current methods of molecularly targeted therapy and the use of tumor biomarkers in the treatment of metastatic colorectal cancer

Despite recent advances in the management of colorectal cancer, metastatic disease remains challenging, and patients are rarely cured. However, a better understanding of the pathways implicated in the evolution and proliferation of cancer cells has led to the development of targeted therapies, that is, agents with action directed at these pathways/features. This approach is more specific to cells within which these pathways, such as epidermal growth factor receptor (EGFR), are overactive; this is in contrast to the relatively indiscriminate mechanism by which cytotoxic chemotherapy tends to affect rapidly dividing cells, regardless of their role. Although factors unique to a given patient, such as the location of the primary tumor (sidedness) or the presence of mutations that confer resistance, may limit the utility of these agents, targeted therapies are now a part of the treatment paradigm for metastatic colorectal cancer, and survival outcomes have significantly improved. This review provides an overview of the role of targeted therapy in the management of patients with colorectal cancer metastases as well as a discussion of issues in patient selection, with a focus on inhibitors of angiogenesis, EGFR-targeted therapy, BRAF mutation–targeted therapies, and other novel strategies, including immunotherapy.     

Clinical management of metastatic colorectal cancer in the era of precision medicine

Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause of cancer deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in approximately 20% of patients. Moreover, up to 50% of patients with localized disease eventually develop metastases. Appropriate clinical management of these patients is still a challenging medical issue. Major efforts have been made to unveil the molecular landscape of mCRC. This has resulted in the identification of several druggable tumor molecular targets with the aim of developing personalized treatments for each patient. This review summarizes the improvements in the clinical management of patients with mCRC in the emerging era of precision medicine. In fact, molecular stratification, on which the current treatment algorithm for mCRC is based, although it does not completely represent the complexity of this disease, has been the first significant step toward clinically informative genetic profiling for implementing more effective therapeutic approaches. This has resulted in a clinically relevant increase in mCRC disease control and patient survival. The next steps in the clinical management of mCRC will be to integrate the comprehensive knowledge of tumor gene alterations, of tumor and microenvironment gene and protein expression profiling, of host immune competence as well as the application of the resulting dynamic changes to a precision medicine-based continuum of care for each patient. This approach could result in the identification of individual prognostic and predictive parameters, which could help the clinician in choosing the most appropriate therapeutic program(s) throughout the entire disease journey for each patient with mCRC. CA Cancer J Clin. 2022;72:000-000.     

晚期大肠癌化学治疗的新进展

近10年先后批准了6个新药用于治疗晚期大肠癌，包括伊立替康、卡培他滨、奥沙利铂、贝伐单抗、西妥昔单抗和帕妥尼单抗，新的治疗方案也不断涌现。与单用氟尿嘧啶一样，晚期大肠癌患者同样可从这3个细胞毒药物和3个靶向药物中获益。大量研究证实，随着这些新的药物和方案的应用，晚期大肠癌的中位生存期可以从最好支持治疗的6～8个月延长到联合化疗加靶向药物的30个月以上。本文试对晚期大肠癌化学治疗的新进展进行一个综述性评价。     

Cetuximab in metastatic colorectal cancer

Management of metastatic colorectal cancer has evolved in the last 10 years, with the availability of targeted therapies resulting in improvement in quality of life and overall survival. Cetuximab is a chimeric monoclonal antibody that binds to the EGF receptor, and the net effects are inhibition of tumor growth, invasion, angiogenesis and metastasis. Cetuximab binding to the EGF receptor is also known to augment the effects of chemotherapy and radiotherapy. Only tumors expressing wild-type KRAS respond to cetuximab and improvements in progression-free survival and overall survival are seen, whereas patients with mutant KRAS are considered to be resistant. Cetuximab is currently available worldwide for use as monotherapy or in combination with chemotherapy in first-, second- or third-line settings in metastatic colorectal cancer patients with wild-type KRAS.     

DC-CIK过继性免疫疗法联合化疗治疗转移性结直肠癌患者的疗效

目的： 研究DC-CIK（dendritic cell-cytokine induced killer cell）过继性免疫治疗联合化疗对转移性结直肠癌（metastatic colorectal cancer,mCRC）的疗效及安全性。 方法： 选取2010年11月至2011年11月在大连市中心医院治疗的80例mCRC患者,40例行DC-CIK治疗联合化疗（联合组）,40例行单纯化疗（化疗组）,评价两组患者治疗后免疫功能、疗效、毒副反应和生活质量（quality of life,QOL)。 结果： 共完成了160周期DC-CIK治疗,联合组治疗前后外周血T细胞亚群无显著变化（P>0.05）,化疗组治疗后外周血中CD3+、CD3+CD4+、CD3+CD8+、CD3-CD56+细胞比例较治疗前显著下降,且明显低于联合组（P<0.05）;联合组3周期治疗后CD4+ T细胞中IFN-γ水平较治疗前显著升高（P<0.05）,化疗组治疗后IFN-γ、IL-2、TNF-α水平著下降,且明显低于联合组（P<0.05）。联合组和化疗组总有效率（response rate, RR）未见明显差异（37.5% vs 22.5%,P>0.05）;联合组疾病控制率（disease control rate,DCR）明显高于化疗组（77.5% vs 50.0%,P<0.05）。联合组Ⅲ～Ⅳ度白细胞减少及Ⅲ～Ⅳ度迟发性腹泻的发生率明显低于化疗组（17.5% vs 42.5%,5.0% vs 25.0;均P<0.05）,其他相关不良反应无显著性差异,而且对症治疗后均可缓解。联合组患者的中位无进展生存（progression-free survival,PFS）较化疗组患者长（6.5个月 vs 4.5个月,P<0.05）,联合组和化疗组患者的总生存（overall survival,OS）比较差异无统计学意义（P>0.05）。联合组在躯体功能、情绪方面较治疗前明显改善,而且明显好于化疗组（P<0.05）。 结论： DC-CIK过继性免疫治疗联合化疗可以明显改善mCRC患者的免疫功能,提高总体疗效,减轻化疗不良反应,延长无进展生存,改善mCRC患者生活质量。