| Added by | mollevi |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer: evaluation of circulating methylated vimentin |
| Creator | Overman et al. |
| Author | Michael J. Overman |
| Author | Van Morris |
| Author | Helen Moinova |
| Author | Ganiraju Manyam |
| Author | Joe Ensor |
| Author | Michael S. Lee |
| Author | Cathy Eng |
| Author | Bryan Kee |
| Author | David Fogelman |
| Author | Rachna T. Shroff |
| Author | Thomas LaFramboise |
| Author | Thibault Mazard |
| Author | Tian Feng |
| Author | Stanley Hamilton |
| Author | Bradley Broom |
| Author | James Lutterbaugh |
| Author | Jean-Pierre Issa |
| Author | Sanford D. Markowitz |
| Author | Scott Kopetz |
| Abstract | PURPOSE: Hypermethylation of promoter CpG islands (CIMP) has been strongly implicated in chemotherapy resistance and is implicated in the pathogenesis of a subset of colorectal cancers (CRCs) termed CIMP-high. EXPERIMENTAL DESIGN: This phase I/II study in CRC (phase II portion restricted to CIMP-high CRC), treated fluoropyrimidine/oxaliplatin refractory patients with azacitidine (75 mg/m2/day subcutaneously D1-5) and CAPOX (capecitibine and oxaliplatin) every three weeks. RESULTS: Twenty-six patients (pts) were enrolled in this study: 15 pts (12 treated at MTD) in phase I and 11 pts in phase II. No dose limiting toxicities were observed. A total of 14 pts were CIMP-high. No responses were seen. CIMP-high status did not correlate with efficacy endpoints [stable disease (SD) or progression-free survival (PFS)] or baseline vimentin methylation level. Changes in vimentin methylation over time did not correlate with efficacy outcomes. Baseline methylated vimentin correlated with tumor volume (P<0.001) and higher levels of baseline methylation correlated with the obtainment of stable disease (P=0.04). CONCLUSIONS: Azacitidine and CAPOX were well tolerated with high rates of stable disease in CIMP-high pts, but no objective responses. Serum methylated vimentin may be associated with benefit from a regimen including a hypomethylation agent, although this study is not able to separate a potential prognostic or predictive role for the biomarker. |
| Publication | Oncotarget |
| Volume | 7 |
| Issue | 41 |
| Pages | 67495-67506 |
| Date | Oct 11, 2016 |
| Journal Abbr | Oncotarget |
| Language | eng |
| DOI | 10.18632/oncotarget.11317 |
| ISSN | 1949-2553 |
| Short Title | Phase I/II study of azacitidine and capecitabine/oxaliplatin (CAPOX) in refractory CIMP-high metastatic colorectal cancer |
| Library Catalog | PubMed |
| Extra | PMID: 27542211 PMCID: PMC5341892 |
| Tags | Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Azacitidine, Biomarkers, Tumor, Capecitabine, CIMP, colorectal cancer, Colorectal Neoplasms, CpG Islands, Disease-Free Survival, DNA Methylation, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Organoplatinum Compounds, original, Vimentin |
| Date Added | 2018/11/13 - 17:25:56 |
| Date Modified | 2019/05/21 - 14:37:20 |
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