Inter-ethnic variability of S-1 pharmacokinetics (PK) and correlation with CYP2A6 phenotyping

Goh, Brian C.; Soo, Ross A.; Lim, Siak Piang; Zhang, J.; Furuie, Taro; Urrea, P. D.; Rosen, Lee S.

doi:10.1200/jco.2008.26.15_suppl.2507

Cited by 9 publications

(4 citation statements)

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“…Therefore, clinical trials conducted in different regions of the world may enroll patients with heterogeneous biological backgrounds that make the trial results not comparable. In addition, the incidences of genetic polymorphisms of genes involved in drug metabolism, including those for fluoropyrimidines, taxanes, and platinums, also differ between Asian and non-Asian populations [18][19][20]. These differences may result in different drug disposition, tolerance to the same chemotherapeutic agents, and preference of Asian and non-Asian investigators in choosing the optimal combinations.…”

Section: Introductionmentioning

confidence: 99%

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

et al. 2012

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Background The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer. Methods Treatment group-based meta-analysis and metaregression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines. Results Twenty-five trials (8 Asian, 17 Western or international) with 56 treatment groups were analyzed.Asian trials reported a lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffusetype histology, and more frequent use of second-line chemotherapy. Meta-analysis revealed significant heterogeneity both in treatment safety (grade 3-4 neutropenia and diarrhea) and efficacy [6-month progression-free survival (PFS) and 1-year overall survival (OS)]. Meta-regression analyses indicate that Asian trials are associated with an 8.2% lower incidence of grade 3-4 neutropenia and 2.1% lower incidence of grade 3-4 diarrhea. A lower percentage of patients with gastroesophageal junction carcinoma and the use of combination regimens predicted better PFS. The use of second-line chemotherapy predicts better 1-year OS, which will increase by 10% for every 10% increase in patients who received second-line chemotherapy. Conclusion Geographic region (Asian vs. non-Asian) is an independent predictor of safety in systemic therapy for gastric cancer.C. Hsu and Y.-C. Shen contributed equally to this work.Electronic supplementary material The online version of this article

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Section: Introductionmentioning

confidence: 99%

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

et al. 2012

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“…Despite these advantages, S-1 pharmacokinetics is subject to interindividual variability, which is explained by the pharmacogenetics of CYP2A6 ( Goh et al , 2008 ). The variant genotypes of CYP2A6 display decreased baseline enzyme activity, leading to reduced 5-FU formation.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity

Kim

Jang

et al. 2011

Br J Cancer

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Background:Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.Methods:Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m−2), followed by 14-day administration of oral S-1 (40 mg m−2 twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for CYP2A6 polymorphisms (*1, *4, *7, *9 or *10), and pharmacokinetic and clinical parameters compared according to the CYP2A6 genotype.Results:In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC0−24 h of 5-fluorouracil/AUC0−24 h of tegafur) was 1.85-fold higher for the *1/*1 group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (P=0.0740), neutropenia (P=0.396), and clinical efficacy (response rate, P=0.583; PFS, P=0.916) were not significantly associated with CYP2A6 genotype, despite differences in 5-FU exposure.Conclusion:The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. CYP2A6 genotypes are associated with differences in the biotransformation of S-1. However, the impact of the CYP2A6 polymorphism on variations in clinical efficacy or toxicity requires further evaluation.

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“…It should be noted that grade 3/4 diarrhea and hand-foot syndrome observed in our study are less frequent. One possible explanation for this observation is interethnic variability (Goh et al 2008).…”

Section: Discussionmentioning

confidence: 98%

Phase II study of capecitabine plus oxaliplatin (XELOX) as first-line treatment and followed by maintenance of capecitabine in patients with metastatic colorectal cancer

Luo

Wang

et al. 2009

J Cancer Res Clin Oncol

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XELOX is a highly effective first-line treatment for Chinese mCRC patients. The response rate, TTP, and overall survival of patients treated with this regimen are similar to those treated with FU/leucovorin/oxaliplatin. Furthermore, our preliminary data show maintenance therapy with capecitabine for those patients without progressive disease after at least six cycles of XELOX can significantly improve DDC; and further prospective randomized control trial is warranted.

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Inter-ethnic variability of S-1 pharmacokinetics (PK) and correlation with CYP2A6 phenotyping

Cited by 9 publications

References 0 publications

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the CYP2A6 polymorphism on pharmacokinetics and clinical activity

Phase II study of capecitabine plus oxaliplatin (XELOX) as first-line treatment and followed by maintenance of capecitabine in patients with metastatic colorectal cancer

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