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Influence of MSI and 18q LOH markers on capecitabine adjuvant monotherapy in colon cancer patients

Authors Matevska-Geshkovska N, Staninova-Stojovska M, Kapedanovska-Nestorovska A, Petrushevska-Angelovska N, Panovski M, Grozdanovska B, Mitreski N, Dimovski A

Received 22 May 2018

Accepted for publication 24 August 2018

Published 1 November 2018 Volume 2018:11 Pages 193—203

DOI https://doi.org/10.2147/PGPM.S172467

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Martin H. Bluth


Nadica Matevska-Geshkovska,1 Marija Staninova-Stojovska,1 Aleksandra Kapedanovska-Nestorovska,1 Natalija Petrushevska-Angelovska,2 Milco Panovski,3 Biljana Grozdanovska,2 Nenad Mitreski,2 Aleksandar Dimovski1

1Center for Biomolecular Pharmaceutical Analyses, Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia; 2University Clinic for Oncology and Radiotherapy, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia; 3University Clinic for Abdominal Surgery, Ss. Cyril and Methodius University in Skopje, Skopje, Macedonia

Purpose: The aim of this study was to evaluate whether pretreatment analysis of selected molecular markers can be used for the prediction of disease-free survival (DFS)/overall survival (OS) of capecitabine adjuvant monotherapy in colon cancer patients.
Patients and methods: A total of 126 patients enrolled in a capecitabine Phase IV clinical trial were analyzed for microsatellite instability (MSI), 18q loss of heterozygosity (LOH), thymidylate synthase (TYMS) 5′ variable number of tandem repeat (VNTR), and methylene tetrahydrofolate reductase (MTHFR) C677T variants. The significance in predicting 5-year DFS/OS was assessed by Kaplan–Meier and Cox regression analyses.
Results: The MSI-high (MSI-H) genotype was significantly associated with DFS (HR 0.205, 95% CI 0.05–0.88, P=0.033) and OS (HR 0.208, 95% CI 0.05–0.89, P=0.035) compared to the microsatellite stable genotype. In models stratified according to clinicopathologic characteristics, the MSI-H genotype remained a positive predictive factor for DFS/OS only in patients with stage III (P=0.023) and patients with tumors localized proximally to the splenic flexure (P=0.004). Distal colon cancers with 18q LOH have a greater survival rate when treated with capecitabine than patients with stable tumors (81.3% vs 50.0%, HR for relapse 0.348, 95% CI 0.13–0.97, P=0.043). TYMS 5′VNTR and MTHFR C677T variants were not associated with DFS or OS.
Conclusion: MSI and 18q LOH markers have the potential to be utilized in the selection of colon cancer patients eligible for capecitabine adjuvant monotherapy.

Keywords: gastrointestinal cancer, microsatellite instability, 18q allelic imbalance, prognostic marker
 

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