Abstract
BackgroundTo assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.MethodsThe clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.ResultsThe median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, P = 0.049), 86d/237d (P = 0.046) and 201d/388d (P = 0.029), respectively; the response rate (87.5% vs 14.3%, P = 0.01) and median progression-free survival (251d vs 84d, P = 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).ConclusionsIn Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.
Highlights
To assess the role of Thymidine Phosphorylase and b-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel
Capecitabine combined with cisplatin or paclitaxel has been proved to be an effective combination regimen used in patients with advanced gastric cancer as firstline or second-line treatment [13,14,15]
That the target of paclitaxel is b-tubulin, and study had reported that there were rare mutations in btubulin for gastric cancer [29], we considered that the overexpression of TUBB3 was the most probable mechanism of paclitaxel resistance in gastric cancer
Summary
To assess the role of Thymidine Phosphorylase and b-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Capecitabine is an orally-administered chemotherapeutic agent which was designed to generate 5-Fluorouracil (5-FU) preferentially in tumors. It is a prodrug which is converted to 5-FU in the tumors through a pathway with three enzymatic steps and two intermediary metabolites involved in. Capecitabine combined with cisplatin or paclitaxel has been proved to be an effective combination regimen used in patients with advanced gastric cancer as firstline or second-line treatment [13,14,15]
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