Abstract:
BACKGROUND:5-Fluorouracil (5-FU) chemotherapy is associated with severe and unpredictable toxicity in a significant proportion of patients. 5,10-Methylenetetrahydrofolate and 5-fluorodeoxyuridine monophosphate bind to thymidylate synthase and together inhibit its function, resulting in cytotoxicity. We hypothesized that susceptibility to 5-FU toxicity might be related to individual differences in the serum components of folate metabolism affecting intracellular 5,10-methylenetetrahydrofolate levels. PATIENTS AND METHODS:A prospective cohort of chemotherapy-naive colorectal cancer patients scheduled to receive intravenous 5-FU and folinic acid for 5 consecutive days every 4 weeks in both adjuvant and palliative settings was studied. Pretreatment clinical and laboratory data were collected. Biochemical data associated with folate metabolism were also collected. The primary endpoint was the occurrence of grade ≥ 3 toxicity and/or toxicity mandating dose delay or reduction. RESULTS:For the 78 eligible patients studied, multivariable analyses identified only a greater pretreatment serum folate level as an independent predictor of grade ≥ 3 toxicity and/or mandating schedule modification (P = .016). Comparing the patient cohorts among the folate quartile groups revealed increasing toxicity trends in the highest quartile with an odds ratio of 2.58 (P = .19) compared with the combined lower quartiles, and superior relapse-free and overall survival for patients treated in the adjuvant setting. Log-rank analysis showed a significant association between higher folate levels and relapse-free and overall survival. CONCLUSION:The pretreatment serum folate level did not conclusively influence 5-FU toxicity and antitumor efficacy. However, high folate levels showed a trend toward a greater incidence of severe toxicities but also lower rates of disease recurrence and mortality. These results provide promising hypothesis-generating data warranting further investigation. The predictive value of pretreatment folate status should be a priority for study in cancer patients receiving 5-FU-based chemotherapy and should be considered a potentially confounding factor in clinical trials and a modifiable parameter in treatment.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Yan M,Ho C,Winquist E,Jonker D,Rayson D,Stitt L,Tokmakejian S,Tomiak A,Vincent MDdoi
10.1016/j.clcc.2016.06.001subject
Has Abstractpub_date
2016-12-01 00:00:00pages
369-376.e3issue
4eissn
1533-0028issn
1938-0674pii
S1533-0028(16)30075-5journal_volume
15pub_type
杂志文章abstract::Thymidylate synthase (TS) expression has been identified as an important predictor of response to 5-fluorouracil (5-FU). However, there is relatively little information on the heterogeneity of TS mRNA expression between primary and metastatic tumors, as well as differential expression of TS mRNA in metastatic sites. I...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2001.n.017
更新日期:2001-11-01 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:PURPOSE:Capecitabine has shown similar efficacy to 5-fluorouracil (5-FU); a regimen containing 2 weeks of capecitabine/oxaliplatin (CapOx) has demonstrated noninferiority to infusional 5-FU/oxaliplatin/leucovorin (FOLFOX) for the treatment of metastatic colorectal cancer (mCRC). This phase II study explores the efficac...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.021
更新日期:2010-07-01 00:00:00
abstract::Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2009.n.025
更新日期:2009-07-01 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:INTRODUCTION:In studies of colorectal cancer, the elderly have been frequently underrepresented because comorbid conditions and functional status often lead to study exclusion. For elderly patients with an indication for neoadjuvant chemoradiotherapy (nCRT), physicians usually decide using clinical factors whether nCRT...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.03.004
更新日期:2018-09-01 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::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::The standard in rectal cancer has been to add adjuvant radiation therapy to surgery in patients with stage II and III disease. Total mesorectal excision has led to lower local recurrence rates, and, if properly performed, may make adjuvant radiation unnecessary for certain stage II and III patients, such as T3 N0 pati...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2003.n.002
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:As more patients are screened for colorectal cancer a small but significant number of interval cancers develop after colonoscopy for colorectal cancer screening. MATERIALS AND METHODS:We reviewed records of 75,314 adult patients who underwent colonoscopy for screening or diagnostic purposes between 1998 and...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2014.11.001
更新日期:2015-03-01 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:INTRODUCTION:Bevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanc...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2013.11.002
更新日期:2014-03-01 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::Local excision is an alternative approach to radical proctectomy for rectal cancer, but from an oncologic standpoint, it is a compromise, and its role remains controversial. Careful patient selection is essential because local excision is generally considered only for early rectal cancer with no evidence of nodal meta...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2008.n.050
更新日期:2008-11-01 00:00:00
abstract:BACKGROUND:With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear. PATIENTS AND METHODS:Using a populatio...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.10.011
更新日期:2018-03-01 00:00:00
abstract::As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III d...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2006.n.019
更新日期:2006-05-01 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::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::This article reviews the current status of the topoisomerase I (top I) inhibitors in the treatment of gastrointestinal (GI) malignancies. We focus on oral drug administration, the mode of administration that is generally preferred by patients with cancer. However, the great majority of the studies have been performed ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2004.n.017
更新日期:2004-09-01 00:00:00
abstract:BACKGROUND:The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:In the context of a prospective single-arm trial (NC...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clcc.2018.06.003
更新日期:2018-12-01 00:00:00
abstract::Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing va...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.008
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Metastatic colorectal cancer (CRC) outcomes continue to improve, but they vary significantly by race and ethnicity. We hypothesize that these disparities arise from unequal access to care. MATERIALS AND METHODS:The Harris Health System (HHS) is an integrated health delivery network that provides medical car...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2019.09.002
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:In this study, the maximum tolerated dose and toxicity profile of FOLFIRI (infusional fluorouracil [5-FU]/leucovorin/irinotecan) plus gefitinib (an oral inhibitor of the epidermal growth factor receptor) were evaluated as first-line therapy in patients with metastatic colorectal cancer. PATIENTS AND METHODS...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2006.n.037
更新日期:2006-09-01 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:Adenocarcinoma of the vermiform appendix is rare. It constitutes less than 0.5% of all gastrointestinal malignancies. Pathologically, appendiceal neoplasms are categorized into various subtypes depending on cell lineage. PATIENTS AND METHODS:We considered a case series of appendiceal invasive adenocarcinoma...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2014.11.003
更新日期:2015-03-01 00:00:00
abstract:BACKGROUND:ERBB2 amplification occurs in 5% of RAS wild-type metastatic colorectal cancer (mCRC) and it has been shown to be a target for treatment with 2 HER2-directed combinations of trastuzumab and lapatinib or trastuzumab and pertuzumab. We present long-term clinical results of trastuzumab and lapatinib (HERACLES-A...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2020.06.009
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:Anal squamous cell carcinoma (ASCC) is a rare, human papilloma virus-associated cancer. The purpose was to investigate the population-based incidence rates, age and gender distribution, and survival of ASCC. MATERIALS AND METHODS:All primary ASCC in 1987 to 2016 were identified in the Cancer Registry of Nor...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.10.001
更新日期:2019-03-01 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::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:BACKGROUND:Systemic chemotherapy increases the possibility of resection in patients with initially unresectable colorectal cancer (CRC), especially patients with hepatic metastasis. However, the predictive factors and prognosis of conversion to resection after chemotherapy in patients with various organ metastases rema...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.10.002
更新日期:2018-03-01 00:00:00