PMID- 31571407 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1759-7714 (Electronic) IS - 1759-7706 (Print) IS - 1759-7706 (Linking) VI - 10 IP - 11 DP - 2019 Nov TI - ABCB1 polymorphism predicts the toxicity and clinical outcome of lung cancer patients with taxane-based chemotherapy. PG - 2088-2095 LID - 10.1111/1759-7714.13184 [doi] AB - BACKGROUND: Taxane-based chemotherapy is widely used in lung cancer. ABCB1 have a role in the prediction of treatment response and toxicity of chemotherapy in solid tumors. In this retrospective study, we investigated ABCB1 polymorphism on response and toxicity in taxane-based chemotherapy in lung cancer patients. METHODS: A total of 122 lung cancer patients who received taxane-based chemotherapy were included in this study. Fluorescence in situ hybridization (FISH) was used for ABCB1 polymorphism detection. Turbidimetric inhibition immunoassay was used for pharmacokinetic analysis. Statistical analysis was performed using SPSS 20.0. RESULTS: The frequency of the ABCB1 2677 site TT/TG/GG genotype was 32.8%, 43.4% and 23.8%, respectively and the frequency of the 3435 sites the TT/TC/CC genotype was 13.9%, 44.3% and 41.8%, respectively. The occurrence of neurotoxicity was higher in patients who had ABCB1 3435 site mutation (TT 88.2%, TC 22.2%, CC 21.6% P = 0.004). There was no significant difference between ABCB1 genotypes with regard to other chemotherapy-induced toxicity. For non-small cell lung cancer (NSCLC) patients, those harboring ABCB1 2677 and 3435 site wild-type patients had longer median progression-free survival (PFS) in the paclitaxel subgroup (3435 site: TT 3.87 vs. TC 9.50 vs. CC 14.13 months; P < 0.001; 2677 site: TT 4.37 vs. TG 9.73 vs. GG 12.1 months; P = 0.013). The area under the concentration-time curve (AUC) of 20 patients treated with docetaxel increased for ABCB1 mutation subgroups. CONCLUSION: ABCB1 mutation is associated with higher neurotoxicity of taxane-based chemotherapy. It also predicts shorter PFS for NSCLC in paclitaxel-based treatment. CI - (c) 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. FAU - Zhong, Jia AU - Zhong J AUID- ORCID: 0000-0002-0464-3754 AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Guo, Zihan AU - Guo Z AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Fan, Liping AU - Fan L AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhao, Xinghui AU - Zhao X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhao, Bingqing AU - Zhao B AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Cao, Zhigang AU - Cao Z AD - Department of Medical Oncology, Mancheng People's Hospital, Baoding, China. FAU - Cheng, Linlin AU - Cheng L AD - Deportment of Medical Oncology, Dong'e People's Hospital, Liaocheng, China. FAU - Shi, Yuanyuan AU - Shi Y AD - Department of Medical Oncology, Mancheng People's Hospital, Baoding, China. FAU - Li, Xiaoting AU - Li X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhang, Yanhua AU - Zhang Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing, China. FAU - An, Tongtong AU - An T AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Wu, Meina AU - Wu M AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Wang, Yuyan AU - Wang Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhuo, Minglei AU - Zhuo M AUID- ORCID: 0000-0003-2489-7791 AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Li, Jianjie AU - Li J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yang, Xue AU - Yang X AUID- ORCID: 0000-0003-2768-1865 AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Chen, Hanxiao AU - Chen H AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Jia, Bo AU - Jia B AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhao, Jun AU - Zhao J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190930 PL - Singapore TA - Thorac Cancer JT - Thoracic cancer JID - 101531441 RN - 0 (ABCB1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B) RN - 0 (Taxoids) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B/genetics MH - Adult MH - Aged MH - Aged, 80 and over MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics MH - Drug Resistance, Neoplasm MH - Female MH - Humans MH - Lung Neoplasms/*drug therapy/genetics MH - Male MH - Middle Aged MH - Mutation MH - *Polymorphism, Genetic MH - Retrospective Studies MH - Survival Analysis MH - Taxoids/*adverse effects/pharmacokinetics/therapeutic use MH - Treatment Outcome PMC - PMC6825927 OTO - NOTNLM OT - ABCB1 OT - chemotherapy OT - lung cancer OT - pharmacokinetic EDAT- 2019/10/02 06:00 MHDA- 2020/07/28 06:00 PMCR- 2019/11/01 CRDT- 2019/10/02 06:00 PHST- 2019/06/05 00:00 [received] PHST- 2019/08/13 00:00 [revised] PHST- 2019/08/14 00:00 [accepted] PHST- 2019/10/02 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2019/10/02 06:00 [entrez] PHST- 2019/11/01 00:00 [pmc-release] AID - TCA13184 [pii] AID - 10.1111/1759-7714.13184 [doi] PST - ppublish SO - Thorac Cancer. 2019 Nov;10(11):2088-2095. doi: 10.1111/1759-7714.13184. Epub 2019 Sep 30.