Effect of Hydration with Bicarbonate Ringer's Solution on Cisplatin-induced Acute Kidney Injury in Patients with Esophageal Cancer: A Retrospective Cohort Study.

INTRODUCTION: Cisplatin (CDDP) often causes acute kidney injury (AKI), and magnesium supplementation has been suggested to be important in preventing CDDP-induced AKI. Sodium bicarbonate Ringer's solution (BRS) is a crystalloid solution composed of various electrolytes, including Mg2+, and can be generally used to supplement missing extracellular fluid and correct metabolic acidosis; however, the clinical outcomes of hydration with BRS for CDDP-induced AKI remain unclear. In this study, we retrospectively compared the effects of BRS and normal saline for hydration in patients undergoing CDDP treatment. METHODS: We analyzed the incidence rate of AKI (grade ≥ 1), the severity of AKI, the serum magnesium level, and the incidence rate of grade ≥ 3 hematological toxicities (leukopenia, neutropenia, anemia, or thrombocytopenia) following CDDP and fluorouracil (5-FU) administration in 131 in-patients who received CDDP and 5-FU for the first time to treat esophageal cancer. RESULTS: Fifty-six patients (43%) received saline alone, while 75 patients (57%) received BRS for hydration. The incidence rate of AKI (grade ≥ 1) was significantly lower in the BRS group (11%) than that in the saline group (39%, p < 0.001). Moreover, severe AKI (grade ≥ 2) was significantly less common in the BRS group than in the saline group. Although the serum magnesium levels before CDDP administration were not significantly different between the two groups (p = 0.939), the serum magnesium levels on days 2-3 after CDDP administration in the BRS group were significantly higher than those in the saline group (p < 0.001). In contrast, there were no significant differences in the incidence rates of hematological toxicity between the two groups. Multivariate analysis revealed that BRS use was an independent factor that significantly contributed to AKI prevention (odds ratio = 0.061, p < 0.001). CONCLUSION: Hydration with BRS could prevent CDDP-induced AKI in patients with esophageal cancer.

Contribution of human organic anion transporter 3-mediated transport of a major linezolid metabolite, PNU-142586, in linezolid-induced thrombocytopenia.

Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for linezolid-induced thrombocytopenia using two real-world clinical databases and explored its underlying mechanism through in vitro and in vivo experiments. In a retrospective analysis of 150 linezolid-treated patients, multivariate analysis identified coadministration of lansoprazole, a proton pump inhibitor, as a significant independent risk factor for thrombocytopenia (odds ratio: 2.33, p = 0.034). Additionally, analysis of the Food and Drug Administration Adverse Event Reporting System database revealed a reporting odds ratio of thrombocytopenia for lansoprazole of 1.64 (95% CI: 1.25-2.16). In vitro studies showed that the uptake of PNU-142586, a major linezolid metabolite, was significantly higher in human organic anion transporter 3-expressing HEK293 (HEK-hOAT3) cells compared to HEK-pBK cells. The apparent IC50 value of lansoprazole against hOAT3-mediated transport of PNU-142586 was 0.59 ± 0.38 µM. In a pharmacokinetic study using rats, coadministration of linezolid with lansoprazole intravenously resulted in approximately a 1.7-fold increase in the area under the plasma concentration-time curve of PNU-142586, but not linezolid and PNU-142300. Moreover, PNU-142586, but not linezolid, exhibited concentration-dependent cytotoxicity in a human megakaryocytic cell line. These findings suggest that linezolid-induced thrombocytopenia should be due to delayed elimination of PNU-142586. Furthermore, delayed elimination of PNU-142586 due to renal failure and hOAT3-mediated transport inhibition by lansoprazole should exacerbate linezolid-induced thrombocytopenia.

Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

BACKGROUND/AIM: Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. PATIENTS AND METHODS: Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). RESULTS: The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). CONCLUSION: The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.