Xiangxiang Ding1, Wenwei Chen2, Haijian Fan3, Bin Zhu4. 1. First Clinical College, Nanjing Medical University, Nanjing 210029, China; Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China. 2. First Clinical College, Nanjing Medical University, Nanjing 210029, China; Department of Oncology, Nanjing Drum Tower Hospital, Nanjing 210008, China. 3. Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China. 4. Department of Radiology, Nanjing Drum Tower Hospital, Nanjing 210008, China. Electronic address: glyyyxk@163.com.
Abstract
BACKGROUND: The aim of this study was to ascertain whether single nucleotide polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway of gemcitabine, could predict clinical outcomes of cancer patients with gemcitabine-based chemotherapy. METHODS: We searched MEDLINE and EMBASE up to January 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according to the Newcastle-Ottawa Quality Assessment Scale. For each included study, the overall survival (OS), overall response rate (ORR) and toxicities were extracted and pooled using random-effects model. RESULTS: In total, data from 13 studies were included. CDA 208A>G and CDA 435C>T were not included in quantified synthesis due to limited data. CDA 79A>C polymorphism was not significantly associated with OS; however, patients carrying the variant CDA 79C allele were likely to have a poor survival, hazard ratio (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade ≥ 3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe neutropenia (OR=1.313, 95% CI 0.157-10.981). CONCLUSIONS: These results suggest that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine-based chemotherapy and a CDA testing before gemcitabine administration is preferred.
BACKGROUND: The aim of this study was to ascertain whether single nucleotide polymorphisms of cytidine deaminase (CDA), a key enzyme in the metabolism pathway of gemcitabine, could predict clinical outcomes of cancerpatients with gemcitabine-based chemotherapy. METHODS: We searched MEDLINE and EMBASE up to January 2013 to identify eligible studies. A rigorous quality assessment of eligible studies was conducted according to the Newcastle-Ottawa Quality Assessment Scale. For each included study, the overall survival (OS), overall response rate (ORR) and toxicities were extracted and pooled using random-effects model. RESULTS: In total, data from 13 studies were included. CDA 208A>G and CDA 435C>T were not included in quantified synthesis due to limited data. CDA 79A>C polymorphism was not significantly associated with OS; however, patients carrying the variant CDA 79C allele were likely to have a poor survival, hazard ratio (HR)=1.03, 95% CI 0.957-1.27 (AC+CC vs. AA). CDA 79A>C polymorphism did not correlated with ORR, odds ratio (OR)=0.719, 95% CI 0.363-1.425 (AC+CC vs. AA). However, patients with the variant CDA 79C allele would experience more grade ≥ 3 leucopenia (OR=2.933, 95% CI 1.357-6.605) and tended to have more severe neutropenia (OR=1.313, 95% CI 0.157-10.981). CONCLUSIONS: These results suggest that CDA 79A>C polymorphisms is a potential biomarker for toxicity of gemcitabine-based chemotherapy and a CDA testing before gemcitabine administration is preferred.
Authors: R Cohen; L H Preta; V Joste; E Curis; O Huillard; A Jouinot; C Narjoz; A Thomas-Schoemann; A Bellesoeur; M Tiako Meyo; J Quilichini; D Desaulle; I Nicolis; A Cessot; M Vidal; F Goldwasser; J Alexandre; B Blanchet Journal: Br J Clin Pharmacol Date: 2019-01-30 Impact factor: 4.335
Authors: Loren K Mell; Ronghui Xu; Catheryn M Yashar; Michael T McHale; John P Einck; Jyoti Mayadev; Euyhyun Lee; Pratibha Binder; Dominique Rash; Ramez Eskander; Elena S Heide; Steven C Plaxe; Arno J Mundt; Cheryl C Saenz Journal: Int J Radiat Oncol Biol Phys Date: 2020-04-22 Impact factor: 8.013