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

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39 Citations (Scopus)

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/m2 on days 1 and 8) plus S-1 (35 mg/m2 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.

Original languageEnglish
Pages (from-to)2050-2057
Number of pages8
JournalCancer
Volume117
Issue number10
DOIs
Publication statusPublished - 2011 May 15

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docetaxel
Cisplatin
Stomach Neoplasms
Cysteine
Proteins
Hand-Foot Syndrome
Confidence Intervals
Therapeutics
Lethargy
Mucositis
Aptitude
Survival
Anorexia
Neutropenia
Disease-Free Survival
Stomach
Multivariate Analysis
Survival Rate
Quality of Life
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jeung, Hei Cheul ; Rha, Sun Young ; Im, Chong Kun ; Shin, Sang Joon ; Ahn, Joong Bae ; Yang, Woo Ick ; Roh, Jae Kyung ; Noh, Sung Hoon ; Chung, Hyun Cheol. / 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. In: Cancer. 2011 ; Vol. 117, No. 10. pp. 2050-2057.
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title = "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",
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/m2 on days 1 and 8) plus S-1 (35 mg/m2 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.",
author = "Jeung, {Hei Cheul} and Rha, {Sun Young} and Im, {Chong Kun} and Shin, {Sang Joon} and Ahn, {Joong Bae} and Yang, {Woo Ick} and Roh, {Jae Kyung} and Noh, {Sung Hoon} and Chung, {Hyun Cheol}",
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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. / Jeung, Hei Cheul; Rha, Sun Young; Im, Chong Kun; Shin, Sang Joon; Ahn, Joong Bae; Yang, Woo Ick; Roh, Jae Kyung; Noh, Sung Hoon; Chung, Hyun Cheol.

In: Cancer, Vol. 117, No. 10, 15.05.2011, p. 2050-2057.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Jeung, Hei Cheul

AU - Rha, Sun Young

AU - Im, Chong Kun

AU - Shin, Sang Joon

AU - Ahn, Joong Bae

AU - Yang, Woo Ick

AU - Roh, Jae Kyung

AU - Noh, Sung Hoon

AU - Chung, Hyun Cheol

PY - 2011/5/15

Y1 - 2011/5/15

N2 - 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/m2 on days 1 and 8) plus S-1 (35 mg/m2 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.

AB - 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/m2 on days 1 and 8) plus S-1 (35 mg/m2 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.

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