Prophylactic Use of Oral Dexamethasone to Alleviate Fatigue During Regorafenib Treatment for Patients With Metastatic Colorectal Cancer

Fukuoka, Shota; Shitara, Kohei; Noguchi, Masaaki; Kawazoe, Akihito; Kuboki, Yasutoshi; Bando, H.; Okamoto, Wataru; Kojima, Takashi; Doi, Toshihiko; Ohtsu, Atsushi; Yoshino, Takayuki

doi:10.1016/j.clcc.2016.07.012

Cited by 15 publications

(10 citation statements)

References 19 publications

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“…For treatment of fatigue, Elfferich et al (123) showed that treatment with anti-TNFα drugs improved fatigue in sarcoidosis and had significantly better efficacy compared to both control and treatment with prednisone, a more general anti-inflammatory drug. A study in colorectal cancer patients found that prophylactic use of dexamethasone, which has anti-inflammatory effects, led to significantly lower levels of fatigue and better treatment tolerance compared to untreated control patients (125). Patients with RA who were treated with rituximab, an antibody which targets and depletes B cells, have also reported an improvement in fatigue after 1 year of treatment (126).…”

Section: Effects On Depression and Fatigue By Treatment Targeting Thementioning

confidence: 99%

The Role of Inflammation in Depression and Fatigue

2019

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Depression and fatigue are conditions responsible for heavy global societal burden, especially in patients already suffering from chronic diseases. These symptoms have been identified by those affected as some of the most disabling symptoms which affect the quality of life and productivity of the individual. While many factors play a role in the development of depression and fatigue, both have been associated with increased inflammatory activation of the immune system affecting both the periphery and the central nervous system (CNS). This is further supported by the well-described association between diseases that involve immune activation and these symptoms in autoimmune disorders, such as multiple sclerosis and immune system activation in response to infections, like sepsis. Treatments for depression also support this immunopsychiatric link. Antidepressants have been shown to decrease inflammation, while higher levels of baseline inflammation predict lower treatment efficacy for most treatments. Those patients with higher initial immune activation may on the other hand be more responsive to treatments targeting immune pathways, which have been found to be effective in treating depression and fatigue in some cases. These results show strong support for the hypothesis that depression and fatigue are associated with an increased activation of the immune system which may serve as a valid target for treatment. Further studies should focus on the pathways involved in these symptoms and the development of treatments that target those pathways will help us to better understand these conditions and devise more targeted treatments.

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Section: Effects On Depression and Fatigue By Treatment Targeting Thementioning

confidence: 99%

The Role of Inflammation in Depression and Fatigue

2019

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“…To assess the prospective functions of the genes influenced by AMPD2, we selected a total of 50 TCGA-COAD specimens with the highest expression of AMPD2 and 50 TCGA-COAD specimens with the lowest expression of AMPD2, and follow-up biologic function prediction analysis was performed in the abnormally high expression and low expression groups. Gene Ontology (GO)[ 12 ] and Kyoto Encyclopedia of Genes and Genomes (KEGG)[ 13 ] analyses were employed using R software (version 3.6) Bioconductor module. The datasets GSE97023 were downloaded from the Gene Expression Omnibus (GEO) ( )[ 14 ], to analyze RNA-seq baseline data for CRC cell lines.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of AMPD2 indicates poor prognosis in colorectal cancer patients via the Notch3 signaling pathway

Gao¹,

Yan²,

Wang³

et al. 2020

WJCC

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BACKGROUND AMPD2 is a critical enzyme catalyzing smooth muscle energy supply and metabolism; however, its cellular biological function and clinical implication in colorectal cancer (CRC) are largely unknown. AIM To clarify the role of AMPD2 in CRC and study the pathway and prognostic value of its role. METHODS AMPD2 expression was analyzed by integrated bioinformatics analysis based on TCGA data sets and immunohistochemistry in tissue microarrays, and the correlation between AMPD2 expression and clinicopathological parameters, Notch3 expression, and prognostic features was assessed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then performed to investigate the regulatory pathway involved. The effects of AMPD2 expression on CRC cells and Notch3 protein expression were investigated by downregulation and overexpression of AMPD2. RESULTS AMPD2 mRNA was significantly overexpressed in tumor tissue when compared with normal tissue in a cohort of the TCGA-COAD data set. Biological function enrichment analysis indicated that the Notch pathway strongly correlated with AMPD2 expression, and that the expression of Notch3 and JAG2 mRNA was positively associated with AMPD2 in CRC tissues. In vitro , AMPD2 overexpression markedly reduced Notch3 protein expression in CRC cells, while knockdown of AMPD2 showed the opposite findings. In addition, protein expression was significantly up-regulated in our CRC cohort as indicated by tissue microarray analysis. High expression of AMPD2 protein correlated with advanced depth of tumor and poor differentiation. Furthermore, high AMPD2 expression in CRC tissues was an indicator of poor outcome for CRC patients. CONCLUSION AMPD2 is commonly overexpressed in CRC, and acts as a metabolism oncogene to induce CRC progression through the Notch signaling pathway. Thus, AMPD2 may be a novel prognostic biomarker for CRC.

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“…Our study demonstrated that 2 mg/day DEX is effective in improving regorafenib-related fatigue and/or malaise without increasing corticosteroid-related toxicity. Fukuoka et al [19] recently conducted a retrospective study evaluating the prophylactic use of DEX (2 mg/day; at the investigator’s discretion) for fatigue during regorafenib treatment in patients with mCRC. They found that the incidence of fatigue (grade ≥1) was lower in the DEX group (25.8%) than in the no-DEX group (50.0%), though the difference was not significant ( p = 0.09).…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402)

et al. 2018

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Background: Regorafenib is an oral multikinase inhibitor with a proven survival benefit for metastatic colorectal cancer patients. The KSCC1402/HGCSG1402 study investigated the prophylactic effect of oral dexamethasone (DEX) on regorafenib-related fatigue and/or malaise. Patients and Methods: Patients who progressed after standard chemotherapy were randomized 1: 1 to a DEX group (2 mg/day; days 1–28) with regorafenib or a placebo group with regorafenib. The primary endpoint was the incidence of fatigue and/or malaise, based on version 4.0 of the National Cancer Institute’s CTCAE (Common Terminology Criteria for Adverse Events). One of the secondary endpoints was the incidence of fatigue and/or malaise based on the CTCAE assessed by patient-reported outcome (PRO). Results: The incidence of any grade of fatigue and/or malaise assessed by the investigators was 58.8% in the DEX group and 61.1% in the placebo group (p = 0.8101), and that assessed by PRO was 47.2 and 58.3%, respectively (p = 0.3450). The incidence of grade ≥2 fatigue and/or malaise, as assessed by the investigators, was 19.4% for the DEX group and 38.9% for the placebo group (p = 0.0695), and that assessed by PRO was 27.8 and 52.8%, respectively (p = 0.0306). Conclusion: Our results suggest that prophylactic oral DEX is clinically effective in improving regorafenib-related fatigue and/or malaise.

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Prophylactic Use of Oral Dexamethasone to Alleviate Fatigue During Regorafenib Treatment for Patients With Metastatic Colorectal Cancer

Cited by 15 publications

References 19 publications

The Role of Inflammation in Depression and Fatigue

The Role of Inflammation in Depression and Fatigue

Overexpression of AMPD2 indicates poor prognosis in colorectal cancer patients via the Notch3 signaling pathway

Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402)

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