Treatment options for metastatic colorectal cancer in patients with liver dysfunction due to malignancy

Faugeras, Laurence; Dili, Alexandra; Druez, Anne; Krug, Bruno; DeCoster, Carolyn; D’Hondt, Lionel

doi:10.1016/j.critrevonc.2017.03.029

Cited by 24 publications

(13 citation statements)

References 62 publications

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“…Important laboratory test for liver function screening includes blood platelet count, (pre-)albumin, bilirubin, international normalized ratio (INR) and enzyme tests including alanine aminotransferase (ALT), serum aspartate (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LD) (24). Impairment of liver function can be seen in patients with liver tumors, either due to the underlying liver disease (25), or due to the tumor burden itself in which case the prognosis is very poor (26,27). Tumors of the liver can be described as either being primary or secondary.…”

Section: The Liver and The Tumorsmentioning

confidence: 99%

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

et al. 2018

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Background Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings. Purpose To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child-Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade. Material and Methods Forty-nine patients with Child-Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade. Results There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7-62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. Conclusion P-ALBI grade 1 and 2 differentiated survival in Child-Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.

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Section: The Liver and The Tumorsmentioning

confidence: 99%

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

et al. 2018

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“…Colorectal cancer (CRC) is a multifactorial disease concerning environmental, lifestyle, genetic, or other risk factors [ 1 ], and it has posed a formidable potential threat to public health owing to its high morbidity and mortality [ 2 ]. Treatment strategies for CRC include surgery, chemotherapy, radiotherapy, targeted therapies, and immunotherapy [ 3 – 5 ]. The therapies for CRC have been well developed in recent decades [ 6 ]; nevertheless, its mortality remains relatively high as a result of frequent recurrence and metastasis [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

Liu

Zhang

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Background As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC) remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW) has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

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“…Except for patient L6, plasma levels of total bilirubin (5.0–20.2 μkat/L), alanine aminotransferase (0.29–0.55 μkat/L), aspartate aminotransferase (0.32–0.47 μkat/L), and alkaline phosphatase (0.61–1.80 μkat/L), all of which provide information about liver functions, were within the physiological range in all patients. In patient L6, total bilirubin level was twice increased (48.9 μmol/L) along with a 3.6-times elevated level of conjugated bilirubin (12.3 μmol/L), which suggests the presence of intrahepatic biliary obstruction caused by ongoing malignancy [16]. The level of γ-glutamyltransferase (0.35–1.97 μkat/L) exceeded the physiological range 1.1–2.9-times in six out of the ten patients.…”

Section: Resultsmentioning

confidence: 99%

Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver

Šadibolová

Zárybnický

Smutný

et al. 2019

IJMS

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Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) on the expression of four phase I DMEs (cytochrome P450 3A4 and 2C, carbonyl reductase 1, and aldo-keto reductase 1C) at both the mRNA and protein levels. For this purpose, human precision-cut liver slices (PCLS) prepared from 10 patients and transfected HepG2 cells were used. Western blotting, quantitative real-time PCR and reporter gene assays were employed in the analyses. In the reporter gene assays, all sesquiterpenes significantly induced cytochrome P450 3A4 expression via pregnane X receptor interaction. However in PCLS, their effects on the expression of all the tested DMEs at the mRNA and protein levels were mild or none. High inter-individual variabilities in the basal levels as well as in modulatory efficacy of the tested sesquiterpenes were observed, indicating a high probability of marked differences in the effects of these compounds among the general population. Nevertheless, it seems unlikely that the studied sesquiterpenes would remarkably influence the bioavailability and efficacy of concomitantly administered drugs.

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Treatment options for metastatic colorectal cancer in patients with liver dysfunction due to malignancy

Cited by 24 publications

References 62 publications

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver

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