期刊
ONCOLOGIST
卷 23, 期 7, 页码 762-+出版社
WILEY
DOI: 10.1634/theoncologist.2018-0037
关键词
-
类别
资金
- Gateway for Cancer Research
- Alex's Lemonade Stand Center of Excellence Grant
Background. Organic cation transporter 2 (OCT2), which is a cisplatin uptake transporter expressed on renal tubules and cochlear hair cells but not on osteosarcoma cells, mediates cisplatin uptake. Pantoprazole inhibits OCT2 and could ameliorate cisplatin ototoxicity and nephrotoxicity. Using a randomized crossover design, we evaluated audiograms, urinary acute kidney injury (AKI) biomarkers, and glomerular filtration rate (GFR) estimated from cystatin C (GFR(cysC)) in patients receiving cisplatin with and without pantoprazole. Materials and Methods. Cisplatin (60 mg/m2 3 2 days per cycle) was administered concurrently with pantoprazole (intravenous [IV], 1.6 mg/kg over 4 hours) on cycles 1 and 2 or cycles 3 and 4 in 12 patients with osteosarcoma (OS) with a median (range) age of 12.8 (5.6-19) years. Audiograms, urinary AKI biomarkers, and serum cystatin C were monitored during each cycle. Results. Pantoprazole had no impact on decrements in hearing threshold at 4-8 kHz, post-treatment elevation of urinary AKI biomarkers, or GFR(cysC) (Fig. 1, Table 1). Histological response (percent necrosis) after two cycles was similar with or without pantoprazole. All eight patients with localized OS at diagnosis are alive and in remission; three of four patients with metastases at diagnosis have died. Conclusion. Pantoprazole did not ameliorate cisplatin ototoxicity or nephrotoxicity. The decrease in GFR(cysC) and increase in N-acetyl-beta-glucosaminidase (NAG) and creatinine demonstrate that these biomarkers can quantify cisplatin glomerular and proximal tubular toxicity. OCT2 inhibition by pantoprazole did not appear to alter antitumor response or survival.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据