title: Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients.
abstract: OBJECTIVE
  A phase II and pharmacokinetic study was designed to assess the efficacy and toxicity profile of an epidophyllotoxin analogue, GL331, in previously treated Chinese gastric cancer patients, with concurrent pharmacokinetic evaluation of the drug's metabolism.
  
  
  METHODS
  GL331 was given at 200 mg/m(2) as a daily 3-h infusion for 5 days every 4 weeks.
  
  
  RESULTS
  Enrolled in the study were 15 patients. One patient died from neutropenic sepsis before evaluation, one patient did not receive the full dose for reasons unrelated to GL331, nine patients had progressive disease with a median survival of 80 days, and five had stable disease with a median survival of 240 days. Grade 3 and 4 myelosuppression occurred in 10 of the 15 patients, with one death from neutropenic sepsis. This patient's peak GL331 concentration was 16.8 microg/ml, which was high compared to the mean peak drug concentration of 6+/-4.1 microg/ml. The mean systemic GL331 clearance was 12.1+/-7.2 l/h per m(2), much lower than 23.3+/-8.2 l/h per m(2) found in the phase I trial. Topoisomerase IIalpha was determined by immunohistochemistry and overexpression was detected in 3 of 11 specimens.
  
  
  CONCLUSIONS
  GL331 was ineffective at this dose and schedule in this group of patients in spite of adequate blood levels of the drug.
authors.affiliation: Division of Cancer Research, National Health Research Institutes, Veterans General Hospital-Taipei, Shipai Road, Taipei, Taiwan.
authors.forename: Jacqueline Ming
authors.initials: JM
authors.lastname: Liu
authors.forename: Li Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.forename: Anna F Y
authors.initials: AF
authors.lastname: Li
authors.forename: Chew Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: Tai-Shun
authors.initials: TS
authors.lastname: Liu
authors.forename: Her Shiong
authors.initials: HS
authors.lastname: Shiah
authors.forename: Jang Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Jong Dong
authors.initials: JD
authors.lastname: Chen
authors.forename: Hsiao Wei
authors.initials: HW
authors.lastname: Wu
authors.forename: Wei Chun
authors.initials: WC
authors.lastname: Lin
authors.forename: Chieh
authors.initials: C
authors.lastname: Lan
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D005047:Etoposide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D004268:DNA-Binding Proteins; C121391:GL 331; D005047:Etoposide; D004250:DNA Topoisomerases, Type II