Abstract：
:Colorectal cancer (CRC) is the second most common cause of cancer-related death in the United States. Despite excellent prognosis for early stage disease, 5-year survival rates in metastatic disease remain low. A small subset of CRC is defined by a deficiency in mismatch repair (dMMR) resulting in high levels of microsatellite instability and are responsive to immunotherapy. Immune checkpoint inhibitors (ICIs) targeting the programmed death 1 (PD-1)/programmed death ligand 1 axis and cytotoxic T-lymphocyte antigen 4 have been explored and show robust clinical outcomes with prolonged progression-free survivals in nonrandomized single-arm clinical trials. On the basis of these data, single-agent therapy with pembrolizumab and nivolumab and combination therapy with nivolumab/ipilimumab have been approved by the US Food and Drug Administration for metastatic CRC that has progressed after treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Ongoing clinical trials are exploring the use of these agents in earlier lines of therapy such as first-line metastatic therapy and adjuvant therapy for stage III CRC. However, resistance to ICIs does occur in a subset of patients and ongoing clinical trials are exploring novel approaches in these PD-1-refractory patients. The aim of this review is to outline the development and decision-making of ICIs in the treatment of dMMR CRC and to discuss ongoing clinical trials in this therapeutic space.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Thomas J,Leal A,Overman MJdoi
10.1016/j.clcc.2020.02.002subject
Has Abstractpub_date
2020-06-01 00:00:00pages
73-81issue
2eissn
1533-0028issn
1938-0674pii
S1533-0028(20)30006-2journal_volume
19pub_type
杂志文章,评审abstract：UNLABELLED:Patients with colorectal cancer (CRC) and renal cell carcinoma (RCC) may be at risk for additional primary malignancies. A review of 101 patients with these concurrent diagnoses was performed. Forty-two percent of patients had 1 or more additional malignancies; none appeared to be associated with Lynch syndr...
journal_title：Clinical colorectal cancer
pub_type： 临床试验,杂志文章
doi：10.1016/j.clcc.2012.07.004
更新日期：2013-03-01 00:00:00
abstract：INTRODUCTION:Coronary vasospasm associated with fluoropyrimidine (FP)-based chemotherapy is a potentially serious complication and reported to occur more often with infusional 5-fluorouracil (5-FU) or capecitabine than with bolus 5-FU. Given the additional benefit of oxaliplatin over FP alone in the management of color...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2018.09.006
更新日期：2019-03-01 00:00:00
abstract：BACKGROUND:Köhne prognostic score is used to classify patients with metastatic colorectal cancer (mCRC) as high, intermediate, or low risk. Using data from 2 phase III trials, we analyzed survival in patients categorized according to Köhne prognostic category and virus-induced rapidly accelerated fibrosarcoma murine sa...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2017.09.006
更新日期：2018-03-01 00:00:00
abstract：:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal cancer of teh gastrointestinal tract. They are characterized by the expression of KIT. Therapeutically, metastatic GISTs are effectively treated by imatinib, a tyrosine kinase inhibitor (TKI) with activity against KIT and platelet-derived growth f...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/ccc.2006.s.005
更新日期：2006-11-01 00:00:00
abstract：BACKGROUND:Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2018.10.002
更新日期：2019-03-01 00:00:00
abstract：BACKGROUND:Similar epidemiologic characteristics suggest a common etiology for colon cancer (CC) and diverticular disease of the colon (DD). The relationship between the 2 diseases is still unclear, and the impact of DD in patients diagnosed with CC on disease-free survival (DFS) and overall survival (OS) is unknown. N...
journal_title：Clinical colorectal cancer
pub_type： 临床试验,杂志文章
doi：10.3816/ccc.2006.n.031
更新日期：2006-07-01 00:00:00
abstract：:Colorectal cancer (CRC), one of the most common malignancies worldwide, is often diagnosed at an advanced stage, and resistance to chemotherapeutic and existing targeted therapy is a major obstacle to its successful treatment. New targets that offer alternative clinical options are therefore urgently needed. Recently,...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.1016/j.clcc.2016.06.006
更新日期：2017-03-01 00:00:00
abstract：BACKGROUND:Anterior resection syndrome (ARS) is common after sphincter-saving surgery for rectal cancer. It includes changes in the frequency and urgency of bowel movements and fecal incontinence. The therapeutic efficacy of biofeedback on ARS is unclear. We sought to evaluate the effectiveness of biofeedback therapy i...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2015.11.002
更新日期：2016-09-01 00:00:00
abstract：:The use of adjuvant chemotherapy has improved survival in early-stage colon cancer. Ongoing adjuvant clinical trials are evaluating the addition of targeted therapies to standard chemotherapy regimen. Preliminary results with bevacizumab were disappointing. Also, cetuximab added to chemotherapy does not seem to be bet...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.3816/CCC.2010.n.039
更新日期：2010-12-01 00:00:00
abstract：BACKGROUND:Few clinical studies have investigated the association between neutrophil-lymphocyte ratio (NLR) and treatment with cetuximab-based chemotherapy in metastatic colorectal cancer (mCRC). The NLR may reflect immune cells modulating specific cytokine signals in the tumor microenvironment; however, which immune-r...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2018.08.002
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:Colorectal cancer (CRC) is a common malignancy. There is growing evidence that CRC incidence is increasing in the younger population. There is controversy surrounding the prognosis of young patients with CRC. In this study we reviewed Australian patients with metastatic CRC (mCRC) who were younger than 40 ye...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2015.07.005
更新日期：2016-03-01 00:00:00
abstract：BACKGROUND:The primary objective of this study was to determine the long-term outcome of sphincter preservation with preoperative radiation therapy (RT) and surgical resection in the treatment of distal rectal adenocarcinoma. PATIENTS AND METHODS:Between April 1988 and December 1996, 36 (cT2, n=9; cT3, n=27) patients ...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.3816/CCC.2006.n.012
更新日期：2006-03-01 00:00:00
abstract：BACKGROUND:Treatment sequencing for patients with refractory metastatic colorectal cancer (mCRC) has been highly debated. The thymidine-based nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib have demonstrated clinical benefits in randomized phase III trials compared with placebo. Ho...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2018.05.012
更新日期：2018-12-01 00:00:00
abstract：:Adjuvant therapy can reduce the risk of disease recurrence in patients with stage II-IV colorectal cancer. Recently, 3 monoclonal antibodies have been shown to improve clinical outcome in this group of patients. Bevacizumab is an antiangiogenesis agent that has been shown in clinical and preclinical models to reverse ...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/CCC.2007.n.004
更新日期：2007-01-01 00:00:00
abstract：BACKGROUND:As of 2006, bevacizumab was available for the treatment of metastatic colorectal cancer (mCRC) in British Columbia (BC). This study compares survival between referred patients diagnosed with mCRC in 2003/2004 (pre-bevacizumab era) and 2006 (bevacizumab era). PATIENTS AND METHODS:The BC cancer agency (BCCA) ...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2011.03.004
更新日期：2011-06-01 00:00:00
abstract：:Significant advances have been made with respect to our understanding of the critical role of agents targeting angiogenic pathways in the treatment of metastatic colorectal cancer (mCRC). The approval of 3 agents that target angiogenic signaling, bevacizumab, ziv-aflibercept, and regorafenib, provides strong evidence ...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.1016/j.clcc.2014.02.001
更新日期：2014-09-01 00:00:00
abstract：:Epidermal growth factor receptor (EGFR) has been validated as an important target in the treatment of metastatic colorectal cancer (mCRC). While initial studies focused on the treatment of disease that was refractory to available chemotherapy agents, 2 recent themes have emerged: the use of KRAS mutation status to sel...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/CCC.2010.s.006
更新日期：2010-06-01 00:00:00
abstract：:The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal can...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/ccc.2004.s.002
更新日期：2004-06-01 00:00:00
abstract：BACKGROUND:The optimal therapeutic strategy for metastatic colorectal cancer patients is still a matter of debate. There are no prognostic variables indicating how many lines individual patients ought to receive, and whether later lines could be effective even when earlier ones were not. PATIENTS AND METHODS:We retros...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2017.03.019
更新日期：2017-12-01 00:00:00
abstract：:The discovery of the key role of the epidermal growth factor receptor (EGFR) and its downstream signaling effectors in the pathophysiology of colorectal cancer (CRC) has ushered in the clinical use of targeted therapies in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibodies cetuximab and panitu...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.1016/j.clcc.2015.05.006
更新日期：2015-12-01 00:00:00
abstract：:Replacing infusional 5-fluorouracil (5-FU) leucovorin (LV) with oral capecitabine would be more convenient to patients, because it would lead to reduced hospital chair time and infusion-related toxicities. Previous trials with oral capecitabine-based regimens (other than XELOX [capecitabine/oxaliplatin]) have failed t...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.3816/CCC.2006.n.044
更新日期：2006-11-01 00:00:00
abstract：:Thymidylate synthase (TS) is a key enzyme in the synthesis of 2'-deoxythymidine-5'-monophosphate, an essential precursor for DNA biosynthesis. For this reason, this enzyme is a critical target in cancer chemotherapy. As the first TS inhibitor in clinical use, 5-fluorouracil (5-FU) remains widely used for the treatment...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/CCC.2002.n.003
更新日期：2002-02-01 00:00:00
abstract：PURPOSE:Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin. DESIGN:This is an extensive literature review of levoleucovorin use in patients with gastrointestinal...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/CCC.2009.n.034
更新日期：2009-10-01 00:00:00
abstract：BACKGROUND:Initial treatment with either neoadjuvant chemoradiation (CRT) or induction FOLFOX (5-Fluorouracil, leucovorin, and oxaliplatin) chemotherapy followed by CRT is considered standard treatment for locally advanced rectal cancer. We compared patient-reported outcomes (PRO) during CRT in patients who had receive...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2019.04.001
更新日期：2019-09-01 00:00:00
abstract：:Regimens based on flouropyrimidines (eg, 5-fluorouracil [5-FU] and capecitabine) are the mainstay of chemotherapy for several malignancies, including colon, pancreatic, upper gastrointestinal, and breast cancers. Warfarin is one of the most commonly used oral anticoagulants. Patients receiving concomitant capecitabine...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/ccc.2005.n.028
更新日期：2005-09-01 00:00:00
abstract：OBJECTIVE:The purposes of this study were to confirm the definite metastasis and micrometastasis rate of upward and lateral lymph nodes of mid-to-low rectal cancer at stage II and stage III, and to evaluate the feasibility and safety of laparoscopic radical correction combined with extensive lymphadenectomy and pelvic ...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.1016/j.clcc.2011.03.025
更新日期：2011-09-01 00:00:00
abstract：:In the past 10 years, overall survival and disease-free survival of patients with colorectal cancer (CRC) has improved substantially because of a combination of factors: (1) more accurate staging as a result of advances in imaging technology; (2) refinements in surgical technique; (3) 'curative' metastasectomy for pat...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：10.3816/CCC.2009.n.013
更新日期：2009-03-01 00:00:00
abstract：BACKGROUND:The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. PATIENTS AND METHODS:Patients w...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1016/j.clcc.2018.06.002
更新日期：2018-12-01 00:00:00
abstract：:Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise infusional 5-fluorouracil (5-FU), leucovorin, and irinotecan or oxaliplatin. The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offer...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章,评审
doi：10.3816/CCC.2008.n.015
更新日期：2008-03-01 00:00:00
abstract：PURPOSE:American Society of Clinical Oncology (ASCO) guidelines define high-risk prognostic features (HRFs) in stage II colon cancer and recommend limiting adjuvant chemotherapy to patients with HRFs. We evaluated the extent to which HRFs influenced decisions on adjuvant chemotherapy before and after publication of the...
journal_title：Clinical colorectal cancer
pub_type： 杂志文章
doi：
更新日期：2009-04-01 00:00:00
