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 trial) at 6.7 years (82 months) follow-up and focus on central nervous system (CNS) recurrences. PATIENTS AND METHODS:Patients had histologically confirmed KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive mCRC. HER2 positivity was assessed by immunohistochemistry and in situ hybridization HERACLES diagnostic criteria. Patients were treated with intravenous trastuzumab 4 mg/kg loading dose, then 2 mg/kg once per week, and oral lapatinib 1000 mg per day until disease progression or toxicity. Patients who presented with symptoms or signs of CNS disease received brain computed tomography scan or magnetic resonance imaging. RESULTS:A total of 35 patients received trastuzumab and lapatinib and 32 were evaluable for response. One patient (3%) achieved complete response (CR), 8 (25%) partial response, and 13 (41%) stable disease. Therefore, response rate was 28%. Median progression-free survival was 4.7 months (95% confidence interval [CI] 3.7-6.1). Median overall survival was 10.0 months (95% CI 7.9-15.8). One patient achieved sustained CR still maintained at 7 years of follow-up. Progression in the central nervous system (CNS) occurred in 6 (19%) of 32 patients. CONCLUSIONS:Long-term (6.7 years) follow-up analysis of HERACLES-A supports using of trastuzumab and lapatinib as treatment reference for KRAS wild-type, chemorefractory HER2-positive mCRC. In this subset of patients, prolongation of survival is accompanied by CNS recurrences that will require diagnostic and therapeutic attention in future studies. Clinicaltrials. Gov identifier: NCT 03225937.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Tosi F,Sartore-Bianchi A,Lonardi S,Amatu A,Leone F,Ghezzi S,Martino C,Bencardino K,Bonazzina E,Bergamo F,Fenocchio E,Martinelli E,Troiani T,Siravegna G,Mauri G,Torri V,Marrapese G,Valtorta E,Cassingena A,Cappello Gdoi
10.1016/j.clcc.2020.06.009subject
Has Abstractpub_date
2020-12-01 00:00:00pages
256-262.e2issue
4eissn
1533-0028issn
1938-0674pii
S1533-0028(20)30094-3journal_volume
19pub_type
杂志文章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::Approximately 40% of patients treated with curative intent for colorectal carcinoma eventually recur. In about one third of these patients, the lesion is localized and potentially resectable. Typically, the recurrence is characterized by findings on diagnostic imaging studies and may be accompanied by a rise in the se...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2001.n.012
更新日期:2001-08-01 00:00:00
abstract::Adult intussusception is a rare occurrence and, unlike in childhood, is usually associated with an underlying tumor. Although computed tomography (CT) imaging can identify an intussusception and point toward a cause, diagnosis is challenging if it is only intermittent. When an intussusception presents in the context o...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2008.n.028
更新日期:2008-05-01 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:BACKGROUND:The safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients. PATIENTS AND METHODS:Patients age ≥65 were identified from SEER-Medicare and categorized...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2012.11.004
更新日期:2013-09-01 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: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
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::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::Combination protocols of 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan or oxaliplatin have demonstrated high activity in metastatic colorectal cancer. Capecitabine, an oral 5-FU prodrug, may replace infusional 5-FU/LV in combination protocols with irinotecan or oxaliplatin. We therefore initiated a phase II stud...
journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2004.n.009
更新日期:2004-05-01 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::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::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::Vascular endothelial growth factor (VEGF) is the driving force behind angiogenesis in most solid malignancies. This also holds true for colorectal cancer (CRC), where increased levels of VEGF in primary cancers are associated with increased microvessel density and poor prognosis. These findings have led to preclinical...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2004.s.009
更新日期:2004-10-01 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:UNLABELLED:Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2012.07.005
更新日期:2013-03-01 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::Microbiome (microbiota) is a community of all microorganisms inhabiting a specific site of the body, including pathogens, which distinguishes it from the physiological microflora. Intestinal dysbiosis plays a key role in the development of colorectal cancer. In the process of carcinogenesis, inflammation, immune respo...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2019.07.006
更新日期:2020-03-01 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::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: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
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: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::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: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: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::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::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: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: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