Advances in the treatment of metastatic colorectal cancer

Colorectal cancer represents the third leading cause of cancer mortality in the United States. During the past four decades, 5-fluorouracil (5-FU) has served as the cornerstone of therapy for individuals with advanced colorectal cancer (ACRC). Despite numerous attempts at maximizing efficacy of 5-FU through biochemical modulation, a significant benefit in terms of survival has never been realized. The recent emergence of novel chemotherapeutic drugs employing different mechanisms of action than 5-FU has led to the incorporation of irinotecan (CPT-11) with 5-FU/leucovorin as the new standard first-line regimen for future trials. This review outlines emerging data utilizing oral fluoropyrimidines and other new agents including oxaliplatin, raltitrexed, and eniluracil. Randomized clinical trials are currently underway in an effort to define optimal combination chemotherapy regimens, scheduling of agents, duration of therapy, and choice of therapy using a variety of prognostic molecular markers.     

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。     

2021年晚期结直肠癌治疗研究进展

结直肠癌是全球发病率第三的恶性肿瘤.目前晚期结直肠癌的治疗以化疗为基石.2021年美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)及欧洲肿瘤内科学(European Society of Medical Oncology,ESMO)公布了多项晚期结直肠癌免疫及靶向...     

Bevacizumab in the treatment of metastatic colorectal cancer

Angiogenesis is essential for tumor growth and metastasis, and has become a useful target for novel biological agents. Vascular endothelial growth factor (VEGF) is one of the most important angiogenesis regulators. Bevacizumab is a recombinant humanized anti-VEGF monoclonal antibody recently approved in Europe and the USA for first- and second-line therapy (in combination with chemotherapy) for metastatic colorectal cancer. It has a proven impact on survival, as demonstrated in large Phase III clinical trials. Treatment with bevacizumab is generally well tolerated, with hypertension and arterial thromboembolic events being the main side effects. Currently, its role in the adjuvant setting, in combination with chemotherapy, is being evaluated in large Phase III clinical trials.     

Optimal treatment of metastatic colorectal cancer

Nonmelanoma skin cancer is the most prevalent malignant disease among light-skinned individuals in the USA, accounting for approximately 1 million new cases annually. Solar ultraviolet radiation is known to be the major cause of skin cancer. The idea that diet, particularly dietary fat, may play a role in modulating cancer incidence has been based largely upon indirect epidemiologic evidence. However, few studies have found correlations of dietary fat intake with skin cancer incidence. Nevertheless, a large body of evidence with experimental animals and one clinical intervention trial, the latter avoiding the pitfalls of many epidemiologic investigations, clearly demonstrate that the level of dietary fat intake can have a significant influence on the occurrence of skin cancer in individuals at high risk.     

Optimal treatment of metastatic colorectal cancer

For over 40 years, fluorouracil has been the only drug registered for the treatment of metastatic colorectal cancer. During the past 5 years, combination chemotherapy regimens including either irinotecan or oxaliplatin have proven to be superior to fluorouracil monotherapy in randomized clinical trials, in terms of response rate, progression-free survival and overall survival. Both doublets demonstrated similar efficacy, therefore either combination can be considered standard first-line treatment for metastatic colorectal cancer. Recently, a new orally active fluorouracil analog, capecitabine, and two targeted biological agents, cetuximab and bevacizumab, have been added to the armamentarium of drugs active against metastatic colorectal cancer, thus making the scenario more complex. Moreover, ongoing clinical trials are currently testing new promising molecularly targeted agents. Thus, we are facing a new era in which the rapid clinical development of novel agents is outpacing the ability to perform Phase III clinical trials. At present, there is no single standard treatment suitable for all patients. However, general principles of management can be derived from the available clinical data in order to guide the therapeutic choice and individualize treatment.     

Advances in the therapy of BRAFV600E metastatic colorectal cancer

ABSTRACT

Introduction: BRAF^V600E metastatic colorectal cancer (CRC) is an aggressive tumor subset with an approximate 8% incidence. In these patients, standard chemotherapy has limited efficacy, and the recent development of novel-targeted treatment regimens may significantly improve clinical outcome.

Area covered: This review provides an overview of available data regarding advances in the first–line treatment of BRAF^V600E metastatic CRC including patient tumors with microsatellite instability. The implications of BRAF^V600E in earlier stage CRC are also discussed.

Expert opinion: Recently, significant progress has been achieved in improving tumor response rates using a novel-targeted regimen in patients with BRAF^V600E metastatic CRC. The implications of BRAF^V600E in non-metastatic CRC are also becoming more evident and remains an area of ongoing investigation. The majority of CRCs with microsatellite instability high are sporadic and frequently harbor BRAF^V600E. All patients with microsatellite instability high metastatic CRCs, irrespective of BRAF^V600E, are candidates for immune checkpoint inhibitors. The optimal sequencing of treatment regimens for patients with BRAF^V600E metastatic CRCs is an important area for future research.     

转移性结直肠癌局部治疗的应用

随着局部治疗的出现,传统医学观念普遍认为不可治愈的转移性结直肠癌患者,部分通过多学科的协作治疗也使得“治愈”变得不再是纸上谈兵。充分利用手术、放疗、射频消融等局部治疗手段,在全身治疗有效的大前提下使得患者达到完全的无瘤状态,从而实现晚期肿瘤患者真正意义上的“治愈”。局部治疗的地位越来越得到重视。本文针对目前在转移性结直肠癌患者中应用的主要局部治疗手段进行综述。     

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。     

Irinotecan for the treatment of metastatic colorectal cancer

In a dozen years of development, irinotecan (CPT11) became one of major therapeutics in the taking care of the metastatic colorectal cancer (CCRM). First used in monotherapy every three weeks, irinotecan has been later developed in association with 5FU and folinic acid according to two modalities of administration (bolus schedule administred weekly or infused schedule every two weeks). This association is now validated both in first and second line. Infused schedule (Folfiri) seems to introduce the best ratio of efficacy/tolerance. The association with the anti VEGF antibody (Avastin), bevacizumab) is promising. Moreover the association of the irinotecan with the anti EGFR antibody (Erbitux)), cetixumab) has show a efficacy in third line after progression under an protocol with irinotecan. Combinations with oxaliplatine (Irox, Irinox) or (Folfoxiri, Folfirinox) still remain in the course of appreciation notably in neoadjuvant context. An increment of dose seems accomplishable in monotherapy or in combination with/AF (high Folfiri doses) with a notable increment of responses rates. Nevertheless this strategy must again show a true clinical interest. Finally they are at promising developments in the fields of the irinotecan pharmacogenetic and pharmacogenomic.     

转移性结直肠癌三线治疗的研究进展*

理想的三线治疗方案应该能够缓解肿瘤的相关症状,提高患者的生活质量。目前转移性结直肠癌的三线治疗尚无标准方案,但已引起关注,本文对相关Ⅱ、Ⅲ期临床研究进行简要评述。     

Bevacizumab-based therapies in the first-line treatment of metastatic colorectal cancer

Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting.     

Novel therapeutic agents in the treatment of metastatic colorectal cancer

Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers (mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.     

Raltitrexed plus oxaliplatin in the treatment of metastatic colorectal cancer

AIMS AND BACKGROUND: As raltitrexed and oxaliplatin (L-OHP) are both effective in the treatment of colorectal cancer but have different mechanisms of action, we studied the antitumoral activity and safety of their combined use in patients with advanced colorectal cancer. METHODS: A 15-min intravenous infusion of raltitrexed (2.5 mg/m2) and a 180-min infusion of oxaliplatin (100 mg/m2) were administered on day 1 every three weeks for a maximum of six cycles. RESULTS: The study involved 51 patients (27 males and 24 females) with a median age of 65 years (range, 43-78); 28 were aged > or = 65 years. The primary tumor site was the colon in 35 patients and the rectum in 16. Thirty-four patients had received prior chemotherapy: 20 as adjuvant treatment and 14 as pretreatment. The most frequent metastatic sites were liver (18 cases), lung (10 cases), liver + lung (8 cases) and lymph nodes (3 cases). Twenty-four patients completed the entire treatment plan. The most common toxicities were transaminitis (16 patients, grade 3-4), diarrhea (six patients, grade 3), nausea/vomiting (one patient, grade 4), and asthenia (one patient, grade 3). The treatment was stopped in one patient because of prolonged grade 4 transaminitis. The adverse event profile was similar in the patients aged > 65 years and < 65 years. Complete responses were observed in 2 patients, partial responses in 12, stable disease in 23, and progression in 8. CONCLUSIONS: The results of the study suggest that the raltitrexed plus oxaliplatin regimen is feasible and clinically active in advanced colorectal cancer.     

New drugs for the treatment of metastatic colorectal cancer

Colorectal cancer (CRC) represents one of the most frequent malignancies in terms of incidence and mortality, thus representing the third leading cause of cancer death worldwide. In the last decade, few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis. Unlike other neoplasms, metastatic CRC patients who have exhausted treatment options often still maintain a good performance status. There are many challenges to increasing potential treatment options, notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure. The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology. This article discusses the main limitations in the development of new drugs and potential future scenarios. In particular, we addressed three questions: (1) The main limitations of targeted therapy in the treatment of metastatic CRC (mCRC); (2) New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy; and (3) Future directions.     

贝伐单抗联合XELOX方案治疗转移性结直肠癌的研究进展

结直肠癌(Colorectal cancer,CRC)是常见的消化系统恶性肿瘤,近几十年来其发病率和死亡率在全球范围内呈上升趋势。目前,在进展期结直肠癌的治疗中,化疗仍起重要作用,靶向治疗为患者带来新的希望,而且随着新一代化疗药物和靶向药物广泛应用于临床,患者生存质量得到了极大的改善,生存期得到了显著延长,靶向联合化疗也已成为转移性结直肠癌治疗研究热点之一。奥沙利铂+卡培他滨(XELOX)作为一线化疗方案治疗转移性结直肠癌(mCRC)能取得很好的疗效,副作用轻,患者耐受良好;贝伐单抗作为一种新型靶向抗肿瘤药物,在抑制肿瘤组织生长和降低肿瘤细胞血行转移率方面显示出良好的效果。贝伐单抗联合XELOX方案治疗mCRC已被广泛研究报道,本文就对其疗效及安全性进行简要综述。