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Combination of low-dose docetaxel and standard-dose S-1 for the treatment of advanced gastric cancer: efficacy, toxicity, and potential predictive factor

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Abstract

Aim

The aim of this study was to evaluate the efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with advanced or recurrent gastric cancer and to investigate whether the protein expression level of dihydropyrimidine dehydrogenase is a predictive factor of toxicities or responses.

Methods

Between March 2010 and December 2011, 61 patients from the Department of Medical Oncology of Shanghai Zhong Shan Hospital, Fudan University, were enrolled in the study. Patients with advanced or recurrent gastric adenocarcinoma were treated with docetaxel of 40 mg/m2 intravenously on day 1 and S-1 of 80 mg/m2 orally on days 1–14 every 3 weeks as first-line chemotherapy. The chemotherapeutic effects were evaluated following every 3 cycles of chemotherapy using the Response Evaluation Criteria In Solid Tumors (RECIST). The serum of peripheral blood was obtained at the start of the study and at each evaluation point to analyze the protein expression level of DPD, which was estimated using an enzyme-linked immunosorbent assay. All the patients were followed-up until the time of progression, death, or the censor time, to calculate progression-free survival and overall survival (OS) time.

Results

In total, 61 patients [median age 60 years (range 28–76 years)] received a total of 318 treatment cycles [median 5 (range 2–9)], and 94 cycles of single S-1 maintenance treatment. One complete response (CR) and 25 partial responses (PR) were observed, with an overall response rate of 42.6 %. A total of 29 patients (47.5 %) had stable disease (SD) and 6 patients (9.8 %) had progressive disease (PD). The disease control rate (DCR, CR + PR + SD) was 90.2 %. Median overall survival was 13.0 months [95 % confidence interval (CI) 10.76–15.24 months], and median PFS was 6.0 months (95 % CI 4.61–7.39 months). Progression-free survival was far longer in peritoneal metastatic patients than that in patients with other metastases (7.3 ± 2. 6 vs. 5.4 ± 2.8 months; P < 0.05); however, this was not the case for OS. Grade 3–4 neutropenia was well controlled and grade 4 non-hematologic toxicities did not occur. Baseline expression level of DPD was not associated with efficacy. Lower expression level of DPD was correlated with high grade of toxicities (P < 0.05).

Conclusion

This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with advanced or recurrent gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline DPD expression level in the serum is associated with toxicity, but not tumor response.

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Acknowledgments

We would like to thank all the patients and colleagues in our department. We also express gratitude to teacher Hu Meiyu at Biomedical Research Center.

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Authors and Affiliations

  1. Medical Oncology Department, Zhong Shan Hospital, Fudan University, Shanghai, 200052, People’s Republic of China

    Yuehong Cui, Qian Li, Yiyi Yu, Yong Chen, Yi Feng, Yan Wang & Tianshu Liu

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  1. Yuehong Cui
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  2. Qian Li
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  3. Yiyi Yu
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Correspondence to Tianshu Liu.

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Cui, Y., Li, Q., Yu, Y. et al. Combination of low-dose docetaxel and standard-dose S-1 for the treatment of advanced gastric cancer: efficacy, toxicity, and potential predictive factor. Cancer Chemother Pharmacol 71, 145–152 (2013). https://doi.org/10.1007/s00280-012-1991-y

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  • DOI: https://doi.org/10.1007/s00280-012-1991-y

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