Among standard chemotherapy regimens for advanced gastric cancer; capecitabine plus cisplatin (XP) and S-1 plus cisplatin (SP) were comparable in a multicenter randomized phase II trial, XParTS II. This study was designed to identify molecular biomarkers for XP and SP in the trial.
Paraffin-embedded primary tumor specimens were collected in 98 of 116 randomized patients in XParTS II. The mRNA was measured with a real-time PCR for thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and thymidylate synthase (TS), and categorized at median into low or high subgroups in order to analyze their association with efficacy endpoints.
Baseline demographic and clinical characteristics of the subjects were similar to the results of the original trial. There was no significant difference in each marker between XP and SP groups; while TP was higher in samples from patients with measurable lesions, and TS was higher in patients with intestinal type and measurable tumors. In comparison for efficacy between XP and SP groups, there was no interaction for PFS and TTF for each marker. While for OS, OPRT was associated with efficacy of the treatment regimens; for XP vs. SP, hazard ratios were 2.0 and 0.73 for low and high mRNA, respectively (P = 0.098 for interaction).
OPRT is suggested to be a candidate predictive biomarker for the first-line treatment of advanced gastric cancer by XP or SP. Further examination is warranted to confirm these results in other clinical trials and/or cohort studies.
Clinical trial identification
All authors have declared no conflicts of interest.