Capecitabine is one of the most active agents in the treatment of many kinds of solid tumors. However, variability in toxicity and response remains a major problem for patients receiving capecitabine. It is general that there are many factors for individual differences of drugs in clinical application, of which genetic factors accounted for more than 20%. Toxicities of capecitabine, such as diarrhea, hand-foot syndrome or anemia, were evaluated for possible relationship with pharmacogenetic polymorphisms in several pharmacogenomics studies. Due to the levels of evidence of those studies are low and lack of sufficient research data of Chinese, it has the important significance in studying individual differences of capecitabine in toxicities, through the pharmacogenomics research. The aim of this study is to evaluating the association genetic polymorphisms with capecitabine-based chemotherapy toxicities in chinese solid tumor patients. By detecting the gene polymorphism, investigators intend to study the pharmacokinetic/pharmacogenomics (PK-PG) correlation of capecitabine and provide scientific basis for precise medication guide for people to use capecitabine.
Study Type
OBSERVATIONAL
Enrollment
2,200
detection of genotype by next generation sequencing
Peking University First Hospital
Beijing, Beijing Municipality, China
Affiliated Hospital of Academy of Military Medical Sciences
Beijing, Beijing Municipality, China
Fuling Center Hospital of Chongqing City
Chongqing, Chongqing Municipality, China
Henan Cancer Hospital
Zhengzhou, Henan, China
The First Hospital of China Medical University
Shenyang, Liaoning, China
Yantai Yuhuangding Hospital
Yantai, Shandong, China
Yunnan Cancer Hospital
Kunming, Yunnan, China
Incidence of severe diarrhea toxicity
The toxicity induced by capecitabine-based chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Patients with grade 3-4 adverse events will be considered as having severe toxicity. At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.
Time frame: At 1 year
Incidence of severe hand-foot syndrome toxicity
The toxicity induced by capecitabine-based chemotherapy during observation time will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Patients with grade 3-4 adverse events will be considered as having severe toxicity. At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.
Time frame: At 1 year
Incidence of other severe toxicities
The other toxicities induced by capecitabine-based chemotherapy during observation time, including gastrointestinal toxicity, neurotoxicity, hematological toxicity etc., will be estimated on the basis of the National Cancer Institute Common Toxicity Criteria Version 4.03. Toxicities with grade 3-4 will be considered as severe toxicity, except for severe neurotoxicity (grade 2-3). At the end of each cycle (each cycle is 21 days) the grade will be scored. And the severest grade will be recorded and used for analysis.
Time frame: At 1 year
Genotyping
Collect blood specimen, then detect genotype by next generation sequencing.
Time frame: Before chemotherapy
The kinds of the metabolites
Determine the metabolic profiles of capecitabine. This outcome is not applicable to patients retrospectively collected.
Time frame: Pre-dose and 3 hours after the last administration in the first cycle
Area under the curve [AUC]
Determine the AUC of capecitabine and its metabolites. This outcome is not applicable to patients retrospectively collected.
Time frame: Pre-dose and 3 hours after the last administration in the first cycle
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