A feasibility study of adjuvant therapy with capecitabine plus oxaliplatin (XELOX) for the patient with advanced colorectal cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2618630 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant Oxaliplatin and Capecitabine (Xelox) +/- AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox +/-AZD8931 on biological pathways using a unique software-driven solution. Transcriptomic profiles from 25 pre-treatment FFPE OAC biopsies and 17 matched resection specimens, treated with Xelox+AZD8931 (n=16) and Xelox alone (n=9), were analysed using the Almac claraT total mRNA report. Tumour Infiltrating Lymphocytes (TILs) were assessed digitally using QuPath software. Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The Immune High subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The Immune Low cluster was pre-dominantly HER2/EGFR negative and EGFR positivity was associated with the Immune Mixed subgroup. Neoadjuvant therapy induced angiogenesis and EMT signalling and a reduction in DNA repair signatures with AZD8931 also promoting an immunosuppressive microenvironment. OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2 positive/Immune High tumours.
2024-09-01 | E-MTAB-13741 | biostudies-arrayexpress
Project description:Interventions: XELOX Capecitabine:2000mg/m2 d1-14 Oxaliplatin:130mg/m2 d1 Q3w
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Project description:Interventions: adjuvant Xeloda followed by XELOX total 5 course after curative resection of liver metastasis from colorectal carcinoma.
Primary outcome(s): completion rate of adjuvant chemotherapy
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Project description:The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.
2024-06-01 | GSE266932 | GEO
Project description:Background: Capecitabine-based adjuvant chemotherapy is the first-line treatment for patients with colorectal cancer (CRC). Although this therapy generally reduces the incidence of CRC recurrence and mortality, it can cause various chemotherapy-related adverse events (CRAEs), one of the most frequent of which is hand-foot syndrome (HFS). Most of the currently available HFS prediction markers focus on the pharmacokinetic parameters of drugs or their metabolites, yet our understanding of the biomolecular mechanism of HFS remains limited. Methods: We conducted an integrated multi-omics analysis of 63 Chinese patients with colorectal cancer (CRC) who had chemotherapy related adcerse effect (CRAE) records during adjuvant chemotherapy. The metabolomic profiles for each of plasma, urine, and colorectal tissue as well as profiles for colorectal-tissue transcriptomics and genome methylation were analyzed based on samples collected before and during surgery. Results: Susceptibility to HFS was found to be associated with profibrotic changes in several aspects of cellular biochemistry and physiology, characterized by reduced nucleotide salvage (indicating potential tissue damage, elevated spermine release, increased M2 macrophage polarization, and hypermethylation of genes for collagen formation. All these aspects were found to promote fibrosis, even before patients received chemotherapeutic drugs or developed any HFS symptoms. Additionally, we developed and validated relevant biomarkers with reasonably good discrimination performance and a high AUROC (area under the receiver operating characteristic curve) value, i.e., from 0.848 to 1.000. Conclusions: Our results demonstrate that a profibrotic phenotype characterized by multi-omics variation in colorectal tissue, plasma, and urine is closely related to the susceptibility to chemotherapy-induced HFS. Our findings provide a better understanding of the molecular mechanism underlying HFS.
2021-08-27 | GSE171468 | GEO
Project description:Interventions: UFT 300mg per m2 per day and LV 75mg per day for 28 days Oxaliplatin:85mg/m2 day1,15 every 5-weeks for 3-cycle After this therapy, followed by UFT/LV until 1 year
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Study Design: Single arm Non-randomized
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Project description:Background: Capecitabine-based adjuvant chemotherapy is the first-line treatment for patients with colorectal cancer (CRC). Although this therapy generally reduces the incidence of CRC recurrence and mortality, it can cause various chemotherapy-related adverse events (CRAEs), one of the most frequent of which is hand-foot syndrome (HFS). Most of the currently available HFS prediction markers focus on the pharmacokinetic parameters of drugs or their metabolites, yet our understanding of the biomolecular mechanism of HFS remains limited. Methods: We conducted an integrated multi-omics analysis of 63 Chinese patients with colorectal cancer (CRC) who had chemotherapy related adverse effect (CRAE) records during adjuvant chemotherapy. The metabolomic profiles for each of plasma, urine, and colorectal tissue as well as profiles for colorectal-tissue transcriptomics and genome methylation were analyzed based on samples collected before and during surgery. Results: Susceptibility to HFS was found to be associated with profibrotic changes in several aspects of cellular biochemistry and physiology, characterized by reduced nucleotide salvage (indicating potential tissue damage, elevated spermine release, increased M2 macrophage polarization, and hypermethylation of genes for collagen formation. All these aspects were found to promote fibrosis, even before patients received chemotherapeutic drugs or developed any HFS symptoms. Additionally, we developed and validated relevant biomarkers with reasonably good discrimination performance and a high AUROC (area under the receiver operating characteristic curve) value, i.e., from 0.848 to 1.000. Conclusions: Our results demonstrate that a profibrotic phenotype characterized by multi-omics variation in colorectal tissue, plasma, and urine is closely related to the susceptibility to chemotherapy-induced HFS. Our findings provide a better understanding of the molecular mechanism underlying HFS.
2021-08-27 | GSE171550 | GEO