Safety of vancomycin in patients with moderate and severe renal dysfunction.

AIM: The new guidelines in Japan do not recommend a vancomycin (VCM) loading dose for patients with an estimated glomerular filtration rate (eGFR) 30 < and ≤ 80 mL×min-1×1.73m-2 (moderate renal dysfunction) or administration to those with the eGFR < 30 mL×min-1×1.73m-2 (severe renal dysfunction). We investigated the safety and efficiency of VCM in patients with moderate and severe renal dysfunction based on the new guidelines. MATERIALS AND METHODS: The study involved patients admitted to our hospital between April 2014 and March 2018 with an eGFR < 80 mL×min-1×1.73m-2 and treated with VCM. VCM trough concentration and pre- and post-administration renal function were investigated retrospectively. The primary endpoints were the proportion of patients who achieved an effective trough concentration of 10 - 20 µg/mL and rate of acute kidney injury (AKI). RESULTS: We included 64 patients (32 moderate, 32 severe). The mean VCM trough concentration achieved for the first time was 9.3 and 11.6 µg/mL in the moderate and severe renal dysfunction groups, respectively (p = 0.91). The effective trough concentration endpoint was achieved by 50% and 43% of the patients in the severe and moderate renal dysfunction groups, respectively, and no significant difference was found in the AKI rate. The serum creatinine change was significantly different between the groups - the moderate group showed a slight deterioration and the severe renal dysfunction group an improvement. CONCLUSION: It may be necessary to increase the dose for these patients with severe renal dysfunction while implementing a VCM loading dose and monitoring trough concentrations and adverse effects.

[A Cost-effectiveness Analysis of Sunitinib vs. Interferon-alpha in Patient with Advanced Renal Cell Carcinoma in Japan].

Sunitinib has been shown to offer clinical benefits during the treatment of advanced renal cell carcinoma. However, molecular targeting drugs are expensive and can have a significant impact on medical expenses. The purpose of this study was to assess the cost-effectiveness of sunitinib as a first-line therapy compared with interferon-alpha (IFN-α) in metastatic renal cell carcinoma patients. A Markov model was used to show the clinical courses of patients with metastatic renal cell carcinoma who received sunitinib or IFN-α. The transition probabilities and utilities employed in this Markov model were derived from two sources. This study focused on the perspective of public healthcare payer, as only direct medical costs were estimated from the treatment schedule for metastatic renal cell cancer. In the cost-effectiveness analysis, outcomes were valued in terms of life years (LYs) and quality-adjusted life years (QALYs). We calculated the incremental cost-effectiveness ratio (ICER) during the cost-effectiveness analysis. The results were tested using Monte Carlo simulations. Sunitinib and IFN-α treatment resulted in LYs of 2.40 years and 2.03 years, QALYs of 1.58 and 1.25, and expected costs of 13,572,629 yen and 6,083,002 yen, respectively. As a result, the ICER associated with replacing IFN-α with sunitinib was 22,695,839 yen/QALYs. Our results suggest that compared with IFN-α, sunitinib prolongs LYs and QALYs, but the increases in quality achieved by sunitinib are more expensive than those produced by IFN-α.

[Cost effectiveness of chemoradiotherapy with cisplatin/fluorouracil and nedaplatin/fluorouracil for patients with esophageal cancer].

OBJECTIVE: To assess the cost-effectiveness of chemoradiotherapy (CRT) regimens for patients with esophageal cancer, we compared two regimens consisting of 5-fluorouracil (5-FU) and cisplatin (CDDP) or 5-FU and nedaplatin (CDGP) with radiotherapy. METHODS: Medical records of 108 patients with esophageal cancer who received CRT of 5-FU+CDDP (CDDP group) or 5-FU+CDGP (CDGP group) were analyzed. In both groups, most of the patients were men with a pathological diagnosis of squamous cell carcinoma. A Markov model was used to show the clinical courses of esophageal cancer after the CRT therapy. An outcome used for economic evaluation was life year gained (LYG). We calculated the cost per-effectiveness ratio (CER) and incremental cost effectiveness ratio (ICER). Clinical effectiveness and costs in this model were investigated retrospectively, and the costs were estimated from the perspective of the medical institution. Sensitivity analysis was used to check the robustness of this model. RESULTS: In CDDP and CDGP group, LYG was 18.23 and 16.31 years and CER was 270,373 and 406,264 yen/LYG, respectively. As a result, ICER was .883,999 yen/LYG. The sensitivity analysis showed that this model was definitely robust. CONCLUSION: Our results suggested that CDDP could prolong LYG with less cost than CDGP and that CRT of 5-FU and CDDP was markedly cost effective treatment.

Analysis of the Risk Factors for Severe Oral Mucositis in Head and Neck Cancer after Chemoradiotherapy with S-1.

Radiotherapy (RT) and chemoradiotherapy (CRT) is widely accepted as the standard treatment for head and neck cancer (HNC). Oral mucositis (OM) often develops as an adverse reaction in HNC patients that receive RT or CRT involving S-1. However, little is known about the risk factors for OM in HNC patients. We retrospectively evaluated patients' pre-treatment clinical data in order to identify the risk factors for severe OM in HNC patients that are treated with RT or CRT involving S-1. We analyzed the cases of 129 patients who received RT or CRT involving S-1 for HNC. The endpoint of the survey was the occurrence of severe OM (≥grade 2). Risk factors that were significantly related to severe OM were identified using logistic regression analysis. The patients' mean age was 69.3±10.1 years, and 118 (92%) of the patients were male. The primary tumor was located in the oropharynx in 21.7% of cases. Severe OM occurred in 85.0% of cases. In the univariate analysis, the following variables were found to be associated with severe OM: age, the type of radiotherapy, disease stage, and chemotherapy. In the multivariate analysis, the location of the primary tumor and chemotherapy were identified as significant risk factors that contributed independently to the risk of severe OM (p<0.05). Our analysis suggests that cancer of the oropharynx and CRT are important risk factors for severe OM in HNC patients that undergo RT or CRT involving S-1.