Role of targeted therapy in metastatic colorectal cancer

Ohhara, Yoshihito; Fukuda, N.; Takeuchi, Satoshi; Honma, Rio; Shimizu, Yasushi; Kinoshita, Ichiro; Dosaka‐Akita, Hirotoshi

doi:10.4251/wjgo.v8.i9.642

Cited by 86 publications

(78 citation statements)

References 92 publications

(100 reference statements)

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“…However, the majority of patients with metastatic CRC (mCRC) experience a poor survival rate (3,4). A growing body of research has demonstrated the positive effect of molecularly targeted treatment on the survival rate of patients with mCRC, especially with the use of monoclonal antibodies against epidermal growth factor receptor (EGFR) (5,6).…”

Section: Introductionmentioning

confidence: 99%

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

et al. 2017

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Abstract. KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, KRAS codon 12 mutations were more common in female patients (P<0.05). KRAS codon 13 mutations tended to arise in right-sided compared with left-sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with KRAS codon 12 wild-type, codon 12 mutations were markedly correlated with a poorer survival (log-rank P= 0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1. P=0.03; HR=2.621, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples.

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Section: Introductionmentioning

confidence: 99%

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

et al. 2017

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“…These conditions contributed to a complete response of the liver metastases and an overall survival time of 29 months. The literature suggests that the median overall survival time for patients with mCRC, following combinational or sequential use of active drugs and molecules, is ~24 months (26).…”

Section: Discussionmentioning

confidence: 99%

Complete response to capecitabine in a frail, elderly patient with metastatic colorectal cancer: A case report

et al. 2016

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Abstract. The clinical management of frail, elderly patients affected by colorectal cancer (CRC) remains a subject of debate. The present study reports the case of an elderly man with metastatic CRC (mCRC) who was successfully treated with capecitabine. The patient survived for 29 months, thus highlighting its potential activity in terms of obtaining a complete response and high efficacy. A 77-year-old man presented with adenocarcinoma of the rectum with multiple and synchronous liver metastases, in addition to several comorbidities. The patient received single-agent capecitabine chemotherapy (825 mg/mq twice a day) on days 1-14 of a 21-day cycle. Following 12 cycles of well-tolerated therapy, a computed tomography scan revealed a complete response with no evidence of liver metastases. An overall survival of 29 months was documented, and the patient eventually succumbed to a diabetes-related complication. In compromised patients with mCRC, reduced-dose capecitabine is an excellent therapeutic option due to its positive safety profile, activity and efficacy.

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“…At the time of data collection for mCRC diagnosis year 2011, NCCN guidelines recommended testing for the KRAS oncogene only among mCRC patients [14]. However, the evolution of recent research found that mCRC patients with RAS mutations on the KRAS as well as the NRAS oncogene do not respond to anti-EGFR treatment either [15-17]. NCCN currently recommends genotyping tumor tissue for both KRAS and NRAS mutations for mCRC giving a result of either normal (wild-type) and able to receive anti-EGFR treatment; or a mutated status and should not be treated with anti-EGFR treatment [18].…”

Section: Introductionmentioning

confidence: 99%

KRAS testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States

et al. 2017

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Background In 2011, the National Comprehensive Cancer Network (NCCN) recommended KRAS testing for metastatic colorectal cancer (mCRC) patients. Our study assessed KRAS testing prevalence and its association with socio-demographic and clinical factors and examined first-line treatment. Methods Ten state population-based registries supported by Centers for Disease Control and Prevention's (CDC) National Program of Cancer Registries (NPCR) collected detailed cancer information on mCRC cases diagnosed in 2011, including KRAS biomarker testing and first-line treatment from ten central cancer registries. Data were analyzed with Chi-square tests and multivariate logistic regression. Results Of the 3,608 mCRC cases, 27% (n = 992) had a documented KRAS test. Increased age at diagnosis (p < 0.0001), racial/ethnic minorities (p = 0.0155), public insurance (p = 0.0018), and lower census tract education (p = 0.0023) were associated with less KRAS testing. Significant geographic variation in KRAS testing (p < 0.0001) ranged from 46% in New Hampshire to 18% in California. After adjusting for all covariates, age and residence at diagnosis (both p < 0.0001) remained predictors of KRAS testing. Non-Hispanic Blacks had less KRAS testing than non-Hispanic Whites (OR = 0.77, 95% CI = 0.61-0.97). Among those tested and found to have normal (wild-type) KRAS, 7% received anti-EGFR treatment; none received such treatment among those with KRAS mutated gene. Conclusions Despite NCCN guideline recommendations, 73% of mCRC cases diagnosed in 2011 had no documented KRAS test. Disparities in KRAS testing existed based on age, race, and residence at diagnosis. Impact These findings show the capacity of monitoring KRAS testing in the US using cancer registry data and suggest the need to understand the low uptake of KRAS testing, and associated treatment choices during the first year since diagnosis.

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Role of targeted therapy in metastatic colorectal cancer

Cited by 86 publications

References 92 publications

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Complete response to capecitabine in a frail, elderly patient with metastatic colorectal cancer: A case report

KRAS testing and first-line treatment among patients diagnosed with metastatic colorectal cancer using population data from ten National Program of Cancer Registries in the United States

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