TY - JOUR
T1 - Phase II and pharmacokinetic study of GL331 in previously treated Chinese gastric cancer patients
AU - Liu, Jacqueline
AU - Chen, Li
AU - Chao, Yee
AU - Li, Anna
AU - Wu, Chew
AU - Liu, Tai Shun
AU - Shiah, Her
AU - Chang, Jang
AU - Chen, Jong
AU - Wu, Hsiao
AU - Lin, Wei
AU - Lan, Chieh
AU - Whang-Peng, Jacqueline
N1 - Funding Information:
Acknowledgements This study was supported by grants from the National Heal th Research Institutes of Taiwan and the Chen Shuyi Cancer Foundation.
PY - 2002/5/6
Y1 - 2002/5/6
N2 - 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.
AB - 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.
KW - Chinese
KW - Gastric cancer
KW - GL331
KW - Refractory
KW - Topoisomerase IIα
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U2 - 10.1007/s00280-002-0429-3
DO - 10.1007/s00280-002-0429-3
M3 - Article
C2 - 11976838
AN - SCOPUS:0036232644
SN - 0344-5704
VL - 49
SP - 425
EP - 428
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 5
ER -
