Influence of UGT1A1 *6/*28 Polymorphisms on Irinotecan-Related Toxicity and Survival in Pediatric Patients with Relapsed/Refractory Solid Tumors Treated with the VIT Regimen
| Autor: | Juan Wang, Junting Huang, Jia Zhu, Yizhuo Zhang, Xiaoqin Zhu, Yi Que, Zijun Zhen, Lian Zhang, Suying Lu, Feifei Sun, Ruiqing Cai, Dalei Zhou |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Abdominal pain Anemia digestive system Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacogenomics and Personalized Medicine Internal medicine Medicine Risk factor Rhabdomyosarcoma Prospective cohort study Original Research Pharmacology relapsed/refractory solid tumors business.industry irinotecan toxicity Cancer medicine.disease UGT1A1 *6/*28 polymorphism Irinotecan Regimen pediatric 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine medicine.symptom business medicine.drug |
| Zdroj: | Pharmacogenomics and Personalized Medicine |
| ISSN: | 1178-7066 |
| DOI: | 10.2147/pgpm.s292556 |
| Popis: | Xiaoqin Zhu,1,2,* Jia Zhu,1,2,* Feifei Sun,1,2,* Zijun Zhen,1,2 Dalei Zhou,1,3 Suying Lu,1,2 Junting Huang,1,2 Yi Que,1,2 Lian Zhang,1,2 Ruiqing Cai,1,2 Juan Wang,1,2 Yizhuo Zhang1,2 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yizhuo Zhang; Juan Wang Email zhangyzh@sysucc.org.cn; wangjuan@sysucc.org.cnObjective: The association between UGT1A1*6/*28 polymorphisms and treatment outcomes of irinotecan in children remains unknown. This retrospective study investigated the influence of UGT1A1*6/*28 polymorphisms on irinotecan toxicity and survival of pediatric patients with relapsed/refractory solid tumors.Methods: The present study enrolled a total of 44 patients aged younger than 18 years at Sun Yat-sen University Cancer Center between 2014 and 2017.Results: There were 26 boys and 18 girls; the median age at first VIT course was six years (range: 1– 18 years). The tumor types included neuroblastoma (n = 25), rhabdomyosarcoma (n = 11), Wilm’s tumor (n = 4), medulloblastoma (n = 2), and desmoplastic small round cell tumor (n = 2). Overall, 203 courses of VIT regimens were prescribed. Neither UGT1A1*6 nor *28 polymorphisms were associated with the incidence rates of severe (grade III–IV) irinotecan-related toxicities, but tended to reduce the patient overall survival (UGT1A1*6, P = 0.146; UGT1A1*28, P = 0.195). Moreover, patients with mutant UGT1A1*6 genotypes were more likely to develop grade I–IV irinotecan-related diarrhea (P = 0.043) and anemia (P = 0.002). Overall, the UGT1A1*28 polymorphism may play a protective role against irinotecan-related diarrhea and abdominal pain.Conclusion: In relapsed/refractory pediatric solid tumors, the UGT1A1*6 polymorphism was a risk factor of irinotecan-related diarrhea and anemia. The UGT1A1*28 polymorphism may serve a protective role in irinotecan-related abdominal pain and diarrhea. Both mutations had a tendency to be risk factors for survival. Nevertheless, prospective studies are required to verify such conclusions.Keywords: UGT1A1 *6/*28 polymorphism, irinotecan toxicity, pediatric, relapsed/refractory solid tumors |
| Databáze: | OpenAIRE |
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