J Gastric Cancer.  2019 Dec;19(4):408-416. 10.5230/jgc.2019.19.e40.

Choice of Capecitabine or S1 in Combination with Oxaliplatin based on Thymidine Phosphorylase and Dihydropyrimidine Dehydrogenase Expression Status in Patients with Advanced Gastric Cancer

• Xu R
• He X
• Wufuli R
• Su Y
• Ma L
• Chen R
• Han Z
• Wang F
• Liu J

• KMID: 2466029
• DOI: http://doi.org/10.5230/jgc.2019.19.e40

Abstract

PURPOSE
To study the efficacy of capecitabine or S-1 plus oxaliplatin (CAPOX or SOX) for treating thymidine phosphorylase (TP)- or dihydropyrimidine dehydrogenase (DPD)-positive advanced gastric cancer.
MATERIALS AND METHODS
Eighty-six patients with stage IIIC to IV gastric cancer were assessed for TP and DPD expression by immunohistochemistry. The association between CAPOX or SOX efficacy and TP/DPD expression was retrospectively analyzed.
RESULTS
There were no significant differences in the objective remission rate (ORR, 52.27% vs. 47.62%; P>0.05), disease control rate (72.73% vs. 73.81%, P>0.05), progression-free survival (hazard ratio [HR], 1.119; 95% confidence interval [CI], 0.739-1.741; P=0.586), and overall survival (OS; HR, 0.855; 95% CI, 0.481-1.511; P=0.588) between CAPOX and SOX. A higher number of stage IV patients showed TP positivity, while DPD-positive patients predominantly showed intestinal type of gastric cancer. In TP-positive patients, the ORRs associated with CAPOX and SOX treatments were 57.14% and 38.10%, respectively; OS was better with CAPOX than with SOX (HR, 0.447; 95% CI, 0.179-0.978; P=0.046). Among DPD-positive patients, the SOX treatment-associated ORR (60.87%) was significantly higher than the CAPOX treatment-associated ORR (43.48%). Furthermore, SOX treatment resulted in better OS than did CAPOX treatment (HR, 2.020; 95% CI, 1.019-4.837; P=0.049).
CONCLUSIONS
No significant difference in clinical efficacy was found between CAPOX and SOX. TP-positive patients might respond better to CAPOX while DPD-positive patients may respond better to SOX. Our findings might serve as a guide for personalized chemotherapy for gastric cancer.

Keyword

Gastric cancer; Capecitabine; Oxaliplatin; Thymidine phosphorylase; Dihydropyrimidine dehydrogenase

MeSH Terms

Capecitabine*
Dihydrouracil Dehydrogenase (NADP)*
Disease-Free Survival
Drug Therapy
Humans
Immunohistochemistry
Retrospective Studies
Stomach Neoplasms*
Thymidine Phosphorylase*
Thymidine*
Treatment Outcome
Capecitabine
Dihydrouracil Dehydrogenase (NADP)
Thymidine
Thymidine Phosphorylase

Figure

• 

  Fig. 1 Comparison of PFS and OS rates in the patients treated with CAPOX and SOX. (A) PFS rate. (B) OS rate. Horizontal axes: time (weeks); vertical axes: survival rate (%). CAPOX = capecitabine plus oxaliplatin; SOX = S-1 plus oxaliplatin; HR = hazard ratio; CI = confidence interval; PFS = progression-free survival; OS = overall survival.

• 

  Fig. 2 TP and DPD expression in gastric cancer specimens. (A) TP expression is shown in the left panel. (B) DPD expression is shown in the right panel. Positivity was defined as staining of at least 20% of the tumor cells. TP = thymidine phosphorylase; DPD = dihydropyrimidine dehydrogenase.

• 

  Fig. 3 Correlation between TP expression and survival in different regimens. (A) Patients with positive TP expression. (B) Patients with negative TP expression. Horizontal axes: time (weeks); vertical axes: overall survival rate (%). CAPOX = capecitabine plus oxaliplatin; SOX = S-1 plus oxaliplatin; TP = thymidine phosphorylase; OS = overall survival; HR = hazard ratio; CI = confidence interval.

• 

  Fig. 4 Correlation between DPD expression and survival in different regimens. (A) Patients with positive DPD expression. (B) Patients with negative DPD expression. Horizontal axes: time (weeks); vertical axes: OS rate (%). CAPOX = capecitabine plus oxaliplatin; SOX = S-1 plus oxaliplatin; DPD = dihydropyrimidine dehydrogenase; OS = overall survival; HR = hazard ratio; CI = confidence interval.

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