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.     

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。     

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.     

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.     

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.     

Advances in the treatment of metastatic colorectal cancer

The overall 5-year survival rate for patients with metastatic colorectal cancer (CRC) is less than 10%. Median survival with 5-fluorouracil (5-FU)/leucovorin (LV) therapy is approximately 12 months. Recent additions to the chemotherapy armamentarium for this disease have begun to prolong median survival times. In trials in which patients are exposed to all three approved chemotherapy agents, oxaliplatin, irinotecan, and 5-FU/LV, or capecitabine during the course of their disease, median survival has reached 20 months. The addition of oxaliplatin and irinotecan to 5-FU/LV regimens has also led to the maintenance of quality of life for longer intervals than were traditionally observed with 5-FU/LV alone. Current standard first-line regimens for metastatic CRC are FOLFOX (infusional 5-FU/LV with oxaliplatin) and FOLFIRI (infusional 5-FU/LV with irinotecan). The addition of bevacizumab to a two-drug regimen (irinotecan with 5-FU/LV) prolongs median survival to 20 months, with a modest amount of additional toxicity. Improvements in this median survival have not yet been realized with modifications to the current standard regimens; however, the oral agent capecitabine appears to be a reasonable substitute for infusional 5-FU/LV in combination regimens or as a single agent, with the advantage of reducing the inconvenience of the long infusion time. Ongoing investigations will identify a place for capecitabine, epidermal growth factor inhibitors, and new cytotoxics in the treatment of metastatic CRC.     

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。     

Surgical treatment of metastatic lung cancer from colorectal cancers

Based on conclusions obtained after the observation of 61 colorectal cancer patients with a lung metastasis, the resection of lung metastasis as a therapy was evaluated. Among these 61 patients, only 5 patients had been identified as having a lung metastasis at the time of resection of the primary lesion, whereas the other 56 patients developed the lung metastasis after the curative resection of the colorectal cancer. Only one patient with a synchronous lung metastasis and twelve patients (eleven with a solitary metastatic lesion and one with multiple metastatic lesions) with metachronous lung metastasis underwent removal of the lung metastasis. The three-year survival rate was 65.2% in the metachronous group.     

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.     

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...     

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.     

Treatment of metastatic colorectal cancer

The treatment of metastatic colorectal cancer (mCRC) has become increasingly complex and nuanced as treatments have evolved over the last decade. During that time, treatment has evolved from single agent 5-fluorouracil (5FU) chemotherapy to combination chemotherapy, and more recently to the inclusion of monoclonal antibodies. As such, mCRC is evolving into a chronic disease in which the median overall survival (mOS) is in excess of 2 years and the 5-year survival is 10%. This review highlights the chemotherapy advances in the treatment of mCRC and focuses on the antibody therapies that have provided incremental improvements in survival. Additionally, we will discuss the management of resectable and unresectable liver metastases, and directed liver therapies. The treatment of metastatic colorectal cancer (mCRC) has become increasingly complex and nuanced as treatments have evolved over the last decade. During that time, treatment has evolved from single agent 5-fluorouracil (5FU) to combination chemotherapy and more recently the inclusion of monoclonal antibodies. As such, mCRC is evolving into a chronic disease in which the median overall survival (mOS) is in excess of 2 years and the 5-year survival is 10%. This review highlights the chemotherapy advances in the treatment of mCRC and focuses on the antibody therapies that have provided incremental improvements in survival. Additionally, we will discuss the management of resectable and unresectable liver metastases and directed liver therapies.     

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.