Metastatic Colorectal Cancer Clinical Trial
Official title:
Influence of Individual Dosage Selection of Irinotecan (CPT-11) Based on UGT1A1 Genotype on Clinical Outcomes and Pharmacokinetics in Chinese Patients With Metastatic Colorectal Cancer
The purpose of this study is to investigate the influence of dose selection of CPT-11 on toxicity, response and pharmacokinetics according to UGT1A1 genotype in colorectal cancer patients.
Genetic polymorphisms of UGTs result in reduced enzyme activity and increased toxicity.
UGT1A1*28 and UGT1A1*6 are reported to increase CPT-11-related toxicity in Asian patients.
Moreover, the area under concentration curve (AUC) ratio of SN-38G to SN-38 is decreased in
Asian patients having UGT1A1 *28 or UGT1A1*6. This implicated that the current standard dose
of CPT-11 would be overdosing for homozygous UGT1A1*28/*28, *6/*6 or *28/*6 patients.
The study is designed to investigate the role of prospectively dose reduction of CPT-11 in
toxicity, tumor response and pharmacokinetics for homozygous UGT1A1 patients, and compare
these parameters to standard dose of CPT-11 for wild-type, heterozygous or homozygous UGT1A1
patients.
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