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β-Tubulin is a Predictive Marker of Docetaxel Combined with S-1 in Recurrent or Metastatic Gastric Cancer

Yuehong Cui, Rongyuan Zhuang, Qian Li, Shan Yu, Yiyi Yu, Yi Feng, Yan Wang, Xi Guo and Tianshu Liu

Aim: The aim of this study was to evaluate efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with recurrent or metastatic gastric cancer, and to investigate whether β-tubulin protein expression level is a predictive or prognostic factor. Methods: From March 2010 to December 2011, 90 patients from Medical Oncology Department of Shanghai Zhongshan Hospital, Fudan University, were enrolled in this study. Patients with recurrent or metastatic gastric adenocarcinoma were treated with docetaxel of 40 mg/m2 intravenously on day 1 and S-1 of 80 mg/m2 orally for 14 days with one-week intermission as first-line chemotherapy. The chemotherapeutic effects were evaluated every 3 cycles using the Response Evaluation Criteria In Solid Tumors (RECIST1.1). The tumor tissues and the serum of peripheral blood were obtained at the start of the study to analyze the protein expression level of β-tubulin, which were estimated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively. Response and toxicity were analyzed. All the patients were followed-up until the time of progression, death, or the censored time, to calculate progression-free survival (PFS) and overall survival (OS) time. Results: In total, 90 patients (median age: 60.5 years [range: 28–76 years]) received a total of 491 treatment cycles (median: 6 [range: 2–9]) of docetaxel combined with S-1 chemotherapy, and 291 cycles of single S-1- maintenance treatment. Three complete response (CR) and thirty-eight partial responses (PR) were observed, with an overall response rate (ORR) of 45.1%. Median OS was 12.5 months, and median PFS was 7.0 months. PFS and OS in patients with peritoneal metastases were significantly longer compared to patients with other metastatic loci. β-tubulin protein expression levels in tumor tissue and in serum were significantly lower in responders than in nonresponders. Lower expression of β-tubulin protein in serum but not in tumor tissues was associated with more serious toxicities.There was significant correlation between tumor tissues and peripheral blood about the expression of β-tubulin. Peritoneal metastasis was an independent prognostic factor by COX regression. PFS and OS were not correlated with β-tubulin expressive level. Conclusion: This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with recurrent or metastatic gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline expression levels of β-tubulin could predict the response. β- tubulin is a predictive marker.