Capecitabine-Activating Enzyme Levels Prognostic for Metastatic Gastric Cancer Outcomes
XP-treated patients with metastatic gastric cancer who had tumors expressing UCK2 and OPRT above a specific threshold survived longer than patients with lower levels of these biomarkers.
|The following article features coverage from the ESMO World Congress on Gastrointestinal Cancer 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
High levels of the capecitabine-activating enzymes uridine-cytidine kinase 2 (UCK2) and orotate phosphoribosyl transferase (OPRT) were associated with longer time to progression and overall survival (OS) among patients with metastatic gastric cancer undergoing treatment with capecitabine plus cisplatin (XP), according to a study presented at the ESMO World Congress on Gastrointestinal Cancer 2018.1
Previous studies demonstrated that UCK2 protein expression was associated with survival in patients with colorectal cancer treated with 5-fluorouracil.2 The purpose of this study was to determine whether UCT2 and OPRT were prognostic for survival among patients with metastatic gastric cancer receiving treatment with XP.
The study included 116 patients with metastatic gastric cancer who received XP with a median age of 55 years and 64% of whom were male. Tumor tissue was analyzed after microdissection with mass spectrometry for 16 protein biomarkers, including UCK2 and OPRT. All tissue samples expressed OPRT and nearly all expressed UCK2 (98%).
UCK2 protein expression greater than the predefined cutoff of 319 amol/µg was significantly associated with longer time to progression (hazard ratio [HR], 0.60; P = .02) and OS (HR, 0.59; P = .015). Similarly, OPRT tumor expression above the predefined cutoff of 790 amol/µg with prolonged time to progression (HR, 0.58; P = .019) and OS (HR, 0.60; P = .029).
These associations remained significant in a multivariate analysis that adjusted for clinical covariates, including ECOG performance status, metastatic sites, and age and gender.
The authors concluded that “mass spectrometric quantification of these common tumor proteins at diagnosis may improve patient selection for XP.” They also added that validation studies are ongoing.
Read more of Cancer Therapy Advisor's coverage of the ESMO World Congress on Gastrointestinal Cancer 2018 meeting by visiting the conference page.
- An E, Ryu M, Yan D, et al. Predicting survival benefit of capecitabine plus cisplatin in patients with metastatic gastric cancer patients using quantitative proteomics. Ann Oncol. 2018;29 (suppl 5;abstr P-057):v16. doi: 10.1093/annonc/mdy151.057
- Yan D, Hong JH, Lee HY, et al. Selecting patients with stage II/III colorectal cancer for 5-fluorouracil-based adjuvant chemotherapy using proteomic analysis. J Clin Oncol. 2018:36 (suppl 4; abstr 708). doi: 10.1200/JCO.2018.36.4_suppl.708