Juan Gu1,2, Dandan Dong3, Enwu Long2,4, Shiwei Tang2, Suqin Feng2, Tingting Li5, Ling Wang2, Xuehua Jiang6,7. 1. Department of pharmacy, Affiliated hospital of Zunyi Medical University, Guizhou, 563003, China. 2. Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, No. 3, section 17, Renmin South Road, Wuhou District, Chengdu City, 610041, Sichuan, China. 3. Department of Pathology, Sichuan academy of medical sciences, Sichuan province people's hospital, Sichuan, 610072, China. 4. Department of pharmacy, Sichuan academy of medical sciences, Sichuan province people's hospital, Sichuan, 610072, China. 5. Department of pharmacy, People's hospital of Xishuangbanna, Dai Autonomous prefecture, 666100, Yunnan, China. 6. Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, No. 3, section 17, Renmin South Road, Wuhou District, Chengdu City, 610041, Sichuan, China. jxh1013@163.com. 7. School of Pharmacy, Zunyi Medical University, Zunyi, 563006, China. jxh1013@163.com.
Abstract
PURPOSE: To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients. METHODS: This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival. RESULTS: In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30-74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy. CONCLUSIONS: High OCT3 expression in CRC tissues may be a protective factor for CRC patients treated with (m)FOLFOX6.
PURPOSE: To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients. METHODS: This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival. RESULTS: In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30-74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy. CONCLUSIONS: High OCT3 expression in CRC tissues may be a protective factor for CRCpatients treated with (m)FOLFOX6.
Authors: Chiara Grisanzio; Lillian Werner; David Takeda; Bisola C Awoyemi; Mark M Pomerantz; Hiroki Yamada; Prasanna Sooriakumaran; Brian D Robinson; Robert Leung; Anna C Schinzel; Ian Mills; Helen Ross-Adams; David E Neal; Masahito Kido; Toshihiro Yamamoto; Gillian Petrozziello; Edward C Stack; Rosina Lis; Philip W Kantoff; Massimo Loda; Oliver Sartor; Shin Egawa; Ashutosh K Tewari; William C Hahn; Matthew L Freedman Journal: Proc Natl Acad Sci U S A Date: 2012-06-22 Impact factor: 11.205
Authors: James P Maloney; Robert S Stearman; Todd M Bull; David W Calabrese; Megan L Tripp-Addison; Marilee J Wick; Ulrich Broeckel; Ivan M Robbins; Lisa A Wheeler; Joy D Cogan; James E Loyd Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-12-23 Impact factor: 5.464