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Introduction: Cisplatin-associated acute kidney injury (AKI) is the major limitation to the use of cisplatin-based chemotherapy regimens. Serum creatinine as a traditional marker did not increase in a timely enough fashion in AKI patients. Therefore, recently, the novel markers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were considered for early detection of AKI. The aim of this study was to compare the sensitivity and specificity of urinary NGAL and KIM-1 with serum creatinine in cisplatin related AKI., Methods: Patients ≥18 years with solid tumors who received cisplatin-based chemotherapy were included. Urine samples were collected 0, 6 and 24 h after cisplatin infusion and the urinary NGAL, KIM-1, and creatinine concentrations were evaluated. NGAL and KIM-1 concentrations were adjusted based on urine creatinine to eliminate hydration effects. Serum creatinine levels were assessed at the base and 72 h after cisplatin administration., Results: Seven out of the 35 recruited patients (20%) suffered from AKI defined by Acute Kidney Injury Network criteria. In AKI patients, the ratio of urinary KIM-1-creatinine at 24 h compared to baseline (24 h/baseline) and NGAL-creatinine 24 h/baseline were significantly higher than those of non-AKI group ( p  = 0.037 and 0.047 respectively). The area under the receiver-operating characteristic curve for KIM-1-creatinine 24 h/baseline and NGAL-creatinine 24 h/baseline were 0.78 (0.59-0.96, p  = 0.032) and 0.77 (0.57-0.97, p  = 0.036) respectively., Conclusions: Our findings showed that the changes in urinary NGAL-creatinine and KIM-1-creatinine ratios, 24 h after cisplatin administration can be utilized to predict AKI in cisplatin recipients.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment., (Copyright © 2015 John Wiley & Sons, Ltd.)

Introduction: Cisplatin is a widely used chemotherapeutic agent with a major side effect of nephrotoxicity. Delayed increase in serum creatinine after cisplatin injection makes serum creatinine not to be an ideal marker for early detection of cisplatin nephrotoxicity. Recently several new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed for early detection of acute kidney injury (AKI). This study assessed kinetic of urine NGAL-creatinine ratio in patients who received cisplatin-containing chemotherapy., Materials and Methods: Patients with a glomerular filtration rates greater than 45 mL/min who received cisplatin-containing chemotherapy were included. Urine creatinine and NGAL concentrations were measured before cisplatin infusion and 6, 24, 48, and 72 hours after cisplatin administration. To minimize hydration effects, urine NGAL levels were adjusted according to urine creatinine., Results: Twenty-four patients were assessed. According to the Acute Kidney Injury Network criteria, 2 patients (8%) experienced cisplatin-associated AKI. The median increases in urine NGAL-creatinine ratio  were 335% (interquartile range, 320% to 350%) in the patients with AKI and 100% (interquartile range, 73% to 190%) in those without AKI (P = .02) during the first 24 hours after cisplatin administration. A urine NGAL-creatinine ratio greater than 26.9 ng/mg 24 hours after cisplatin infusion had a sensitivity of 86% and a specificity of 50% to detect cisplatin-associated nephrotoxicity., Conclusions: Urine NGAL-creatinine ratio significantly increased in patients with cisplatin-associated AKI. Urine NGAL-creatinine ratio within the first 24 hours after cisplatin infusion may better predict cisplatin-associated nephrotoxicity than serum creatinine level.

Background: Anti-cancer potential of silymarin has been shown in cell culture. However, no prospective clinical study has been conducted in this relation. Methods: In a randomized double blind pilot study, we compared effects of addition of standard chemotherapy along with silymarin (420mg/day) versus placebo on clinical response of advanced tumors after three cycles of cisplatin-based chemotherapy. Results: There was no significant difference in tumor size after three consecutive chemotherapy courses but a trend toward lower metastasis rate in chemotherapy + silymarin group. Concomitant use of silymarin and chemotherapy was very well tolerated but didn't significantly increase clinical response. Conclusion: Due to the trend towards significantly lower metastasis in silymarin group, further study with larger sample size is needed to better clarify probable role of adjunctive therapy with silymarin in patients with solid tumors. [ABSTRACT FROM AUTHOR]

To define efficacy of pre-operative chemotherapy in down staging of advanced non-round cell soft tissue sarcomas. From Sep 2002 to Dec 2005, 70 patients were treated by Ifosfamid, MESNA, cisplatin, adriamycin, mitomycin and subsequent surgery. Postoperatively, patients received radiotherapy in cases of microscopically incomplete resection or local recurrence. The median age of the patients was 34 years and the median tumor size was 14 cm. According to AJCC classification 46 patients had stage 3 and 24 had stage 4 diseases. The most common subtypes were MFH and leiomyosarcoma. The most common sites of tumors were lower extremity and trunk. Toxicity grades three or higher consisted of nausea, Leucopenia and infection. About 50% of the patients received G-CSF. Response to chemotherapy was assessable in 63 patients; 9 patients achieved complete response and 16 showed partial response. Disease progressed in 8 and did not change in 37. The best response was seen with MFH, fibrosarcoma and synovial sarcoma. After chemotherapy seventy percent of patients underwent complete surgery. Disease relapsed in 41 patients and twenty two patients died of metastasis. Median survival of patients was 30 months. IMAP plus G-CSF is safe and effective as preoperative chemotherapy in some subtypes of sarcomas, although the metastasis problem has not been eliminated [ABSTRACT FROM AUTHOR]

Cisplatin-induced nephrotoxicity (CIN) is a major dose-limiting factor in cisplatin use for the management of human cancers. This study was designed to evaluate the effect of melatonin on CIN as the first clinical trial in humans. This pilot, randomized, double-blinded, placebo-controlled clinical trial was conducted with cancer patients. Participants were randomly assigned to receive either 20 mg/day oral melatonin or placebo from 24 to 48 hours before cisplatin therapy. Urine samples were collected at 0, 6 and 24 h following cisplatin infusion to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and creatinine. Serum creatinine (SCr) levels were assessed at baseline and 72 h after cisplatin administration. Fifty-five patients were randomly assigned to receive either melatonin (n = 25) or placebo (n = 30), where 3 (7.5 %) versus 9 (21.4 %) acute kidney injury (AKI) episodes were reported in each group respectively. Although urinary biomarkers increased in both groups, the magnitude of the increase was smaller in the melatonin group compared to placebo. In addition, differences of urine KIM-1/creatinine ratio at 6 h and 24 h from baseline were significantly lower in the melatonin group (2.37(−71.16 to 63.70) ng/mg and −1.45(−80.28 to 48.76) ng/mg) compared to placebo (3.83(−11.19 to 37.05) ng/mg and 0.38(−5.42 to 70.00) ng/mg). This study showed that the number of AKI episodes in patients who received melatonin was lower compared to the placebo group, although it was not found to be statistically significant due to the small sample size. Moreover, melatonin administration in cisplatin recipients reduced tubular kidney injury, evidenced by less increase in KIM-1/creatinine and NGAL/creatinine ratios. [ABSTRACT FROM AUTHOR]