Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer

Clarinda Chua, Iain Beehuat Tan, Yasuhide Yamada, SunYoung Rha, Wei Peng Yong, Whee Sze Ong, Chee Kian Tham, Matthew Ng, David W.M. Tai, Satoru Iwasa, Hwee Yong Lim, Su Pin Choo

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Abstract

Purpose: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. Methods: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m2 on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. Results: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. Conclusion: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

Original languageEnglish
Pages (from-to)397-408
Number of pages12
JournalCancer Chemotherapy and Pharmacology
Volume76
Issue number2
DOIs
Publication statusPublished - 2015 Aug 27

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Epidermal Growth Factor Receptor
Cisplatin
Stomach Neoplasms
Body Surface Area
Esophagogastric Junction
Chemotherapy
Platinum
Stomach
Therapeutics
Drug Therapy
Neoplasms
Survival
Protein Transport
Standard of Care
Treatment Failure
Fluorouracil
Disease-Free Survival
Disease Progression
Labels
Tumors

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Chua, Clarinda ; Tan, Iain Beehuat ; Yamada, Yasuhide ; Rha, SunYoung ; Yong, Wei Peng ; Ong, Whee Sze ; Tham, Chee Kian ; Ng, Matthew ; Tai, David W.M. ; Iwasa, Satoru ; Lim, Hwee Yong ; Choo, Su Pin. / Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer. In: Cancer Chemotherapy and Pharmacology. 2015 ; Vol. 76, No. 2. pp. 397-408.
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abstract = "Purpose: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. Methods: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m2 on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. Results: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 {\%}, with a clinical benefit rate of 66.7 {\%}. Median progression-free survival was 7.4 months; 62.6 {\%} patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. Conclusion: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.",
author = "Clarinda Chua and Tan, {Iain Beehuat} and Yasuhide Yamada and SunYoung Rha and Yong, {Wei Peng} and Ong, {Whee Sze} and Tham, {Chee Kian} and Matthew Ng and Tai, {David W.M.} and Satoru Iwasa and Lim, {Hwee Yong} and Choo, {Su Pin}",
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Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer. / Chua, Clarinda; Tan, Iain Beehuat; Yamada, Yasuhide; Rha, SunYoung; Yong, Wei Peng; Ong, Whee Sze; Tham, Chee Kian; Ng, Matthew; Tai, David W.M.; Iwasa, Satoru; Lim, Hwee Yong; Choo, Su Pin.

In: Cancer Chemotherapy and Pharmacology, Vol. 76, No. 2, 27.08.2015, p. 397-408.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II study of trastuzumab in combination with S-1 and cisplatin in the first-line treatment of human epidermal growth factor receptor HER2-positive advanced gastric cancer

AU - Chua, Clarinda

AU - Tan, Iain Beehuat

AU - Yamada, Yasuhide

AU - Rha, SunYoung

AU - Yong, Wei Peng

AU - Ong, Whee Sze

AU - Tham, Chee Kian

AU - Ng, Matthew

AU - Tai, David W.M.

AU - Iwasa, Satoru

AU - Lim, Hwee Yong

AU - Choo, Su Pin

PY - 2015/8/27

Y1 - 2015/8/27

N2 - Purpose: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. Methods: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m2 on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. Results: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. Conclusion: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

AB - Purpose: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. Methods: We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m2 on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. Results: All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. Conclusion: The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

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