Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer

Taroh Satoh, Yasushi Omuro, Yasutsuna Sasaki, Yasuo Hamamoto, Narikazu Boku, Takao Tamura, Atsushi Ohtsu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: To evaluate the pharmacokinetics (PK) of capecitabine and cisplatin, administered in combination with or without trastuzumab, in Japanese patients with HER2-positive advanced gastric cancer (AGC). Methods: Patients eligible for this PK study (study JP19959), which was carried out during treatment Cycle 1 of the ToGA study, received either capecitabine and cisplatin (XP arm) or trastuzumab plus capecitabine and cisplatin (HXP arm). All patients received capecitabine (1,000 mg/m 2 orally, twice daily for 14 days) and cisplatin (80 mg/m 2 intravenous infusion on Day 1). Patients in the HXP arm also received trastuzumab (8 mg/kg intravenous infusion on Day 1), concurrently with capecitabine. No further study medication was administered during study JP19959. Serial plasma samples for PK analysis were obtained at intervals before and after the administration of capecitabine and cisplatin on Day 1. Results: Twenty-two patients were enrolled in this PK study: eight in the HXP arm and 14 in the XP arm. All blood samples were available for PK analysis. Co-administration of trastuzumab resulted in no statistically or clinically significant changes in the PK profiles of capecitabine or its metabolites, or of cisplatin (total or unbound platinum). Conclusions: Variability in the AUC last and C max values for the capecitabine was consistent with the known PK profile of capecitabine and fell within established limits. Concurrent trastuzumab therapy is unlikely to alter the PK or safety profile of capecitabine or cisplatin in Japanese patients with HER2-positive AGC.

Original languageEnglish
Pages (from-to)949-955
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume69
Issue number4
DOIs
Publication statusPublished - 2012 Apr 1
Externally publishedYes

Fingerprint

Pharmacokinetics
Cisplatin
Stomach Neoplasms
Intravenous Infusions
Trastuzumab
Capecitabine
Metabolites
Platinum
Area Under Curve
Blood
Plasmas
Safety

Keywords

  • Advanced gastric cancer
  • Capecitabine
  • Cisplatin
  • Pharmacokinetics
  • ToGA study
  • Trastuzumab

ASJC Scopus subject areas

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

Cite this

Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer. / Satoh, Taroh; Omuro, Yasushi; Sasaki, Yasutsuna; Hamamoto, Yasuo; Boku, Narikazu; Tamura, Takao; Ohtsu, Atsushi.

In: Cancer Chemotherapy and Pharmacology, Vol. 69, No. 4, 01.04.2012, p. 949-955.

Research output: Contribution to journalArticle

Satoh, Taroh ; Omuro, Yasushi ; Sasaki, Yasutsuna ; Hamamoto, Yasuo ; Boku, Narikazu ; Tamura, Takao ; Ohtsu, Atsushi. / Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer. In: Cancer Chemotherapy and Pharmacology. 2012 ; Vol. 69, No. 4. pp. 949-955.
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T1 - Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer

AU - Satoh, Taroh

AU - Omuro, Yasushi

AU - Sasaki, Yasutsuna

AU - Hamamoto, Yasuo

AU - Boku, Narikazu

AU - Tamura, Takao

AU - Ohtsu, Atsushi

PY - 2012/4/1

Y1 - 2012/4/1

N2 - Purpose: To evaluate the pharmacokinetics (PK) of capecitabine and cisplatin, administered in combination with or without trastuzumab, in Japanese patients with HER2-positive advanced gastric cancer (AGC). Methods: Patients eligible for this PK study (study JP19959), which was carried out during treatment Cycle 1 of the ToGA study, received either capecitabine and cisplatin (XP arm) or trastuzumab plus capecitabine and cisplatin (HXP arm). All patients received capecitabine (1,000 mg/m 2 orally, twice daily for 14 days) and cisplatin (80 mg/m 2 intravenous infusion on Day 1). Patients in the HXP arm also received trastuzumab (8 mg/kg intravenous infusion on Day 1), concurrently with capecitabine. No further study medication was administered during study JP19959. Serial plasma samples for PK analysis were obtained at intervals before and after the administration of capecitabine and cisplatin on Day 1. Results: Twenty-two patients were enrolled in this PK study: eight in the HXP arm and 14 in the XP arm. All blood samples were available for PK analysis. Co-administration of trastuzumab resulted in no statistically or clinically significant changes in the PK profiles of capecitabine or its metabolites, or of cisplatin (total or unbound platinum). Conclusions: Variability in the AUC last and C max values for the capecitabine was consistent with the known PK profile of capecitabine and fell within established limits. Concurrent trastuzumab therapy is unlikely to alter the PK or safety profile of capecitabine or cisplatin in Japanese patients with HER2-positive AGC.

AB - Purpose: To evaluate the pharmacokinetics (PK) of capecitabine and cisplatin, administered in combination with or without trastuzumab, in Japanese patients with HER2-positive advanced gastric cancer (AGC). Methods: Patients eligible for this PK study (study JP19959), which was carried out during treatment Cycle 1 of the ToGA study, received either capecitabine and cisplatin (XP arm) or trastuzumab plus capecitabine and cisplatin (HXP arm). All patients received capecitabine (1,000 mg/m 2 orally, twice daily for 14 days) and cisplatin (80 mg/m 2 intravenous infusion on Day 1). Patients in the HXP arm also received trastuzumab (8 mg/kg intravenous infusion on Day 1), concurrently with capecitabine. No further study medication was administered during study JP19959. Serial plasma samples for PK analysis were obtained at intervals before and after the administration of capecitabine and cisplatin on Day 1. Results: Twenty-two patients were enrolled in this PK study: eight in the HXP arm and 14 in the XP arm. All blood samples were available for PK analysis. Co-administration of trastuzumab resulted in no statistically or clinically significant changes in the PK profiles of capecitabine or its metabolites, or of cisplatin (total or unbound platinum). Conclusions: Variability in the AUC last and C max values for the capecitabine was consistent with the known PK profile of capecitabine and fell within established limits. Concurrent trastuzumab therapy is unlikely to alter the PK or safety profile of capecitabine or cisplatin in Japanese patients with HER2-positive AGC.

KW - Advanced gastric cancer

KW - Capecitabine

KW - Cisplatin

KW - Pharmacokinetics

KW - ToGA study

KW - Trastuzumab

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