Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients

Jacqueline Liu, Li Chen, Yee Chao, Anna Li, Chew Wu, Tai Shun Liu, Her Shiah, Jang Chang, Jong Chen, Hsiao Wu, Wei Lin, Chieh Lan, Jacqueline Whang-Peng

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12 Citations (Scopus)

Abstract

Purpose: 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. Material and methods: GL331 was given at 200 mg/m2 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 μg/ml, which was high compared to the mean peak drug concentration of 6±4.1 μg/ml. The mean systemic GL331 clearance was 12.1±7.2 l/h per m2, much lower than 23.3±8.2 l/h per m2 found in the phase I trial. Topoisomerase IIα 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.

Original languageEnglish
Pages (from-to)425-428
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume49
Issue number5
DOIs
Publication statusPublished - May 6 2002
Externally publishedYes

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Keywords

  • Chinese
  • Gastric cancer
  • GL331
  • Refractory
  • Topoisomerase IIα

ASJC Scopus subject areas

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

Cite this

Liu, J., Chen, L., Chao, Y., Li, A., Wu, C., Liu, T. S., Shiah, H., Chang, J., Chen, J., Wu, H., Lin, W., Lan, C., & Whang-Peng, J. (2002). Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients. Cancer Chemotherapy and Pharmacology, 49(5), 425-428. https://doi.org/10.1007/s00280-002-0429-3