Literature DB >> 21523716

A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy.

Hei-Cheul Jeung1, Sun Young Rha, Chong Kun Im, Sang Joon Shin, Joong Bae Ahn, Woo Ick Yang, Jae Kyung Roh, Sung Hoon Noh, Hyun Cheol Chung.   

Abstract

BACKGROUND: The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes.
METHODS: Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis.
RESULTS: Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis.
CONCLUSIONS: The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer. 2010 American Cancer Society.

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Year:  2010        PMID: 21523716     DOI: 10.1002/cncr.25729

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


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