title: Pharmacokinetic analysis of capecitabine and cisplatin in combination with trastuzumab in Japanese patients with advanced HER2-positive gastric cancer.
abstract: OBJECTIVE
  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.
authors: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Osaka, Japan. taroh@cfs.med.osaka-u.ac.jp
authors: Taroh
authors: T
authors: Satoh
authors: Yasushi
authors: Y
authors: Omuro
authors: Yasutsuna
authors: Y
authors: Sasaki
authors: Yasuo
authors: Y
authors: Hamamoto
authors: Narikazu
authors: N
authors: Boku
authors: Takao
authors: T
authors: Tamura
authors: Atsushi
authors: A
authors: Ohtsu
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007564:Japan; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D002945:Cisplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab