Nephroprotective potential of plant was tested at two different doses in curative. Nat2 polymorphism in omani gastric cancer patientsrisk predisposition and clinicopathological associations. Although it is best known for dna damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic. Sharp april 25, 2016 cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury aki in 30% of patients. Nephrotoxicity is cumulative and often doselimiting. Cellular toxicity cisplatin cisdiamminedichloroplatinum ii cddp is a.
Prevention of cisplatininduced ototoxicity in children. Little is known about the association be tween the rate of cisplatin administration and the severity of cisplatininduced renal damage in children. Cisplatininduced nephrotoxicity causes altered renal. Recently, a liposomal formulation of cisplatin, lipoplatin, was developed to reduce systemic toxicity of cisplatin. Renal and electrolyte disturbances associated with cisplatin. Mar 31, 2015 nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6.
Cisdichlorodiammine platinum ii, or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is. Intravenous route powder for solution administer under the supervision of a. Evidence for nephrotoxicity prevention with cisplatin. Nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. Nov 26, 2007 cisplatin is associated with adverse drug reactions including renal damage and gastrointestinal dysfunction mishima et al. Mean baseline serum creatinine concentration and peak serum creatinine concentration were 0. The initial injury triggers a proliferative response in renal tubular cells, which in the. Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. Nephrotoxicity with cisplatin and antihypertensive medications.
See below for a comprehensive list of adverse effects. Clinical evaluation of tavocept to decrease diuresis time. See full prescribing information for cisplatin injection. Cisplatin dose adjustment in patients with renal impairment. Each of the medications in vip is designed to slow the growth of and kill testicular cancer cells. Pdf effects of different doses of hyperbaric oxygen on. The participation of other enzymes such as aminopeptidase n apn, renal.
Traditional cell culture methods and cytotoxicity assays are well established as in vitro tests for nephrotoxicity but the correlation with in vivo results is extremely poor. Cisplatin cisdichlorodiammineplatinum platinum coordination complex is an effective chemotherapy against a wide spectrum of tumors such as testicular, head and neck, ovarian, lung, cervical, and bladder cancers. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatininduced renal cell death. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinumbased therapeutics. To develop a clinical practice guideline for the prevention of cisplatin induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates. No significant difference in karyolysisapoptosisnecrosis between. To date, although the pathophysiological basis of cisplatin nephrotoxicity has.
One of the limiting side effects of cisplatin use is nephrotoxicity. Cisplatin induced nephrotoxicity an assessment based on. Recent reports have shown that cisplatin induces depletion of mg and that mg supplementation can reduce renal toxicity. Reactive nitrogen species have also been studied in cisplatininduced nephrotoxicity. Blood urea nitrogen bun your bun reflects the amount of nitrogen that is present in your body in the form of a waste product called urea. To evaluate the nephroprotective potential of ethanolic extract of aerial parts of plant scoparia dulcis against cisplatin induced nephrotoxicity in wistar rats.
Nephrotoxicity of cisplatin combination chemotherapy in. However, its clinical use is severely limited by serious sideeffects, of which nephrotoxicity and myelosuppression are considered to be the most important because they significa. More side effects increased nephrotoxicity change in the drug metabolism 4. Cisplatin cisdiamminedichloroplatinumii, cddp is an antineoplastic drug used in the treatment of many solidorgan cancers, including those of the head, neck, lung, testis, ovary, and breast. Original article risk analysis for cisplatininduced.
It is under clinical evaluation in adult medicine, and phase 1 and phase 2 studies showed no nephrotoxicity up to a dose of 125 mgm 2 every 14 days 158, 159. Indianapolis, in, usa according to the manufacturers instruction. Nephrotoxicity may occur in as many as 50% to 75% of patients receiving the drug, and is apparently due to renal tubular injury. Cisplatin is a medicine used alone or with other therapies to treat cancer of the testicles, ovaries, or bladder the drug is also sometimes used offlabel to treat head and neck. Exposure of tubular cells to cisplatin activates signaling pathways that are cell death promoting mapk, p53, ros, and so on or cytoprotective p21. The protective effects of maltol on cisplatininduced nephrotoxicity. N14 received zinc sulfate plus cisplatin based regimen. Chemotherapy and kidney injury american society of. See chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency. Platinum based anticancer drug candidate, with cisplatin, a. Cisplatin is one of the most widely used and most potent chemotherapy drugs.
Mitigation of acute kidney injury by cellcycle inhibitors. Cisplatin based regimen was composed of cisplatin in a dose of 75 mgm2 and other chemotherapeutic agents such as docetaxel, etoposide, 5flourouracil and gemcitabine that had no effect on cisplatininduced nephrotoxicity. Al moundhri ms, al kindi, m, al nabhani m, al bahrani b. Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. N14 received zinc sulfate plus cisplatinbased regimen. The area of most interest in regard to cisplatin nephrotoxicity is the s3 segment of the osompt. Cisplatin, nephrotoxicity, risk factor, intravenous hydration, mannitol introduction cisplatin is an antineoplastic drug that is classi fied as a platinum compound and is used to treat a variety of solid tumors such as lung carcinoma, head and neck cancer, germ cell tumor. Cisplatin enters renal cells by passive andor facilitated mechanisms. You are paged because your patient is unresponsive. This medicine may lower the ability of the bone marrow to make blood cells that the body needs. The cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. Nephrotoxicity is the most wellknown and clinically important toxicity. Acute kidney injury aki is a common clinical condition caused by loss of kidney function.
Cisplatin nephrotoxicity nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. To develop a clinical practice guideline for the prevention of cisplatininduced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates. Cisplatin cddp, an inorganic platinum chemotherapeutic drug, is widely administered either alone or in combination with other agents for the clinical treatment of various solid tumors, including lung, gastric. Nephrotoxicity renal toxicity managing side effects. There are several case reports of adverse cardiac effects of cisplatin due to hydro electrolytic imbalances depleted mg levels owing to nephrotoxicity5. It is used as an antineoplastic agent in the treatment of metastatic tumors of the testis. To determine the incidence and evaluate the risk factors of. Renal toxicity can be minimized by high volume hydration with mannitol diuresis.
A 58yearold man with metastatic bladder cancer was treated with cisplatin, 70 mgm 2 body surface area, intravenously, after hydration with normal saline, 0. Cisplatin nephrotoxicity is the composite result of the transport of cisplatin into renal epithelial cells, injury to nuclear and mitochondrial dna, activation of a multiple cell death and survival pathways and initiation of a robust inflammatory response. Prevention of cisplatininduced ototoxicity in children and. Combining cisplatin with cationized catalase decreases nephrotoxicity while improving antitumor activity sf ma1, m nishikawa2, k hyoudou1, r takahashi3, m ikemura1, y kobayashi1, f yamashita1 and m hashida1 1department of drug delivery research, graduate school of pharmaceutical sciences, kyoto university, sakyoku, kyoto, japan. As a highly effective antineoplastic chemotherapeutic drug, cisplatin is widely used clinically to treat a variety of human malignancies. May use concomitant amifostine to decrease nephrotoxicity. Cisplatin treated homozygous gunn rats showed significantly decreased karyolysisapoptosisnecrosis than the heterozygous gunn rats and the wistar rats in the osompt fig. However, its side effects include nephrotoxicity, neurotoxicity, bone marrow toxicity, gastrointestinal toxicity, and ototoxicity, which can limit its use. Dichloroacetate prevents cisplatininduced nephrotoxicity. Druginduced aki, as observed during cisplatinbased anticancer therapy, is responsible for about 20% of renal failure cases.
Click the orange links and well show you extra information. Patients with preexisting cisplatin induced peripheral neurotoxicity generally do not worsen during carboplatin therapy. Iproplatin was the first quadrivalent platinumiv complex possessing an octahedral configuration, rather than the squareplanar configuration of cisplatin and carboplatin, that entered clinical trials. Cisplatin treatment often produces extensive gastrointestinal side effects, which might lead to more magnesium depletion through anorexia and diarrhea. Cisplatin nephrotoxicity american journal of kidney diseases. Effect of the ethanolic extract of scoparia dulcis in. Cisplatin is the generic name for the trade name drug platinol and platinolaq. Cisplatin induces magnesium depletion, and magnesium deficiency itself may enhance cisplatin nephrotoxicity. Vip etoposideifoscisplatin, testicular chemoexperts. The platinumbased chemotherapy agents cisplatin, carboplatin, and oxaliplatin, used to treat a huge number of cancers including the lung, upper and lower gi, ovarian, and germ cell tumours, are a common cause of renal tubular and glomerular damage, which can be treatmentlimiting. Additional studies with rats have shown that inhibition of ggt with acivicin protected them from cisplatin nephrotoxicity. Cisplatin is a major antineo plastic drug for the treatment of solid tumors, but it has dosedependent renal toxicity.
Cisplatininduced kidney dysfunction and perspectives on. Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Cell and biomarkerbased assays for predicting nephrotoxicity. A urine output of 100 mlhour or greater will tend to minimise cisplatin nephrotoxicity. The chief limit to its greater efficacy is its nephrotoxicity, which has made it necessary both to lower its dosage and actively hydrate patients to reduce it. Pdf prevention of cisplatin nephrotoxicity researchgate. Nephrotoxicity is the main side effect of cisplatin. Dogs receiving tavocept cisplatin and piroxicam had significantly lower nephrotoxicity grade than dogs receiving cisplatin and piroxicam without tavocept p 0. Cisplatin side effects, dosage, interactions drugs. Research article effect of zinc sulfate in protection. Renal tubular dysfunction and a cumulative impairment in renal function, as manifested by a decline in the glomerular filtration rate gfr, can be dose limiting. Cisplatin, which is an inorganic molecule containing a platinum ion, is an antineoplastic agent that has been used to treat various solid tumors. Nauseavomiting, anorexia, impaired fertility myelosuppression is the most common dose limiting toxicity also renal toxicity delayed nadir.
Cisplatin based regimen was composed of cisplatin in a dose of 75 mgm2 and other chemotherapeutic agents such as docetaxel, etoposide, 5flourouracil and gemcitabine that had no effect on cisplatin induced nephrotoxicity. This can be accomplished by prehydration with 2 litres of an appropriate intravenous solution, and similar post cisplatin hydration recommended 2,500 mlm 2 24 hours. Cisplatin and other platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors. Cisplatin and others cisplatin nephrotoxicity robert safirstein, md, jonathan winston, md, marvin goldstein, md, donald moel, md, steven dikman, md, and joseph guttenplan, phd cisdichlorodiammine platinum ii, or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is. Lack of therapeutic options has contributed to high mortality rates in aki patients.
The nephrotoxic effect of cisplatin is cumulative and dosedependent and often necessitates dose reduction or withdrawal. Cisplatin should not be given more frequently than once every 34 weeks. Effects of different doses of hyperbaric oxygen on cisplatininduced nephrotoxicity article pdf available in renal failure 293. Pathophysiology of cisplatininduced acute kidney injury. Research article open access nephrotoxicity of cisplatin combination chemotherapy in thoracic malignancy patients with ckd risk factors ko sato1, satoshi watanabe2, aya ohtsubo1, satoshi shoji1, daisuke ishikawa1, tomohiro tanaka1, koichiro nozaki1, rie kondo1, masaaki okajima1, satoru miura1, junta tanaka3, takuro sakagami1, toshiyuki koya1, hiroshi kagamu1, hirohisa yoshizawa2 and. Evidence for interventions to prevent nephrotoxicity. The use of cisplatin in patients with preexisting renal dysfunction and the renal effects of the platinum analogs, carboplatin and oxaliplatin, are discussed elsewhere. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death. Cisplatin nephrotoxicity can present in a number of ways including hypomagnesaemia, increased serum creatinine and urea. However, the major doselimiting side effect of cisplatin is its nephrotoxicity badary et al. The role of oxidantantioxidant systems in chronic nephrotoxic ity is uncertain. Aug 05, 2015 nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance.
Cisplatin is an anticancer antineoplastic or cytotoxic chemotherapy drug. The renal content of peroxynitrite and nitric oxide is increased in cisplatintreated rats. Developing a more clinicallyrelevant mouse model of. Overview of the pathophysiological events in cisplatin nephrotoxicity. Collectively, these changes lead to acute kidney injury aki 4. While toxicities include ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions 1,2, the main doselimiting side effect of cisplatin is nephrotoxicity 3,4,5. It has been shown that mice deficient in ggt were resistant to the nephrotoxic effects of cisplatin. Even though the establishment of cisplatininduced nephrotoxicity can be alleviated. Cisplatin is a coordinate metal complex with significant antineoplastic activity and various adverse effects, including acute and chronic renal insufficiency and renal magnesium wasting.
Nephrotoxicity is seen in about 20% of patients and frequently limits the clinical use of cisplatin. Cisplatin and magnesium affect the same sodium and water channels in the outer medulla. Cisplatin nephrotoxicity in children after continuous 72h. To view other topics, please sign in or purchase a subscription. T d i i h l l i d to date, it is the only platinum drug. Cisplatin is important chemotherapeutic agents used to treat solid tumors. We hypothesized that mg infusion combined with low volume hydration may not be. Abstract nephrotoxicity is a major doselimiting side effect facing cisplatinbased chemotherapy of a wide variety of cancers. Magnesium supplementation and high volume hydration reduce. Implication for health policypracticeresearchmedical education. Pachrin3, wanhee kim4, cheolyong hwang1, daeyong kim3, hwayoung youn1 and changwoo lee2 1departments of veterinary internal medicine. In some cases, health care professionals may use the trade name platinol and platinolaq, or other names such as cddp, when referring to the generic drug name cisplatin.
Nephrotoxicity is the doselimiting toxicity of cisplatin. Research article effect of zinc sulfate in protection against. Nephrotoxicity is one of the most common kidney problems and occurs when your body is exposed to a drug or toxin that causes damage to your kidneys. Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. Cisdichlorodiammine platinum ii, or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is currently among the most widely used agents in the chemotherapy of cancer. Objective to determine whether appropriate dose adjustment is made in patients with renal impairment using the cockcroftgault cg or the abbreviated modification of diet in renal disease amdrd formulas to estimate the glomerular filtration rate gfr.
Cisplatin for injection, for intravenous use initial u. Numerous compounds have been studied to prevent cisplatin nephrotoxicity but only amifostine is us food and drug ad ministration fda approved for. Clinical evaluation of tavocept to decrease diuresis time and. Your patient is receiving cisplatin and his iv fluids are d5.
Jul 17, 2019 commonly reported side effects of cisplatin include. It remains an important and effective therapy in many forms of cancer today. Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6. Many different drugs and agents may cause nephrotoxic acute kidney injury aki in children. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. Less nephrotoxicity but antitumour activity comparable to that of cisplatin. Druginduced aki, as observed during cisplatin based anticancer therapy, is responsible for about 20% of renal failure cases. Anaesthetic implications of chemotherapy bja education. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Apr 21, 2015 acute kidney injury aki is a common clinical condition caused by loss of kidney function. Nephrotoxicity hepatotoxicity pulmonary fibrosis lomustine altered glucose metabolism streptozocin common. The role of oxidantantioxidant systems in chronic nephrotoxicity is uncertain. Palliative intravenous cisplatin treatment for concurrent. Cisplatin dosing, indications, interactions, adverse.
Although recovery can occur after one episode of cisplatininduced aki, studies have indicated multiple episodes may lead to the. In childhood aki, incidence, prevalence, and etiology are not well defined. Highlights of prescribing information these highlights do not include all the information needed to use cisplatin injection safely and effectively. Laboratory study lrnf effects of different doses of. Cisplatin is the most widely used antineoplastic agent for most of the tumors like lung cancer, gastric cancers, ovarian cancer, penile cancer, cervical cancer and many other. Cisplatin 1 mgml sterile concentrate summary of product. Nephrotoxicity of cancer treatment in children medscape. Jan 17, 2014 background nephrotoxicity is the doselimiting side effect of cisplatin justifying the assessment of renal function for dose adjustment. Nephrotoxicity may also be referred to as renal toxicity. Cisplatin nephrotoxicity is clearly doserelated and used to be considered dose limiting. Numerous studies have demonstrated that several mechanisms, including oxidative stress, dna damage, and inflammatory res ponses, are closely associated with cisplatininduced nephrotoxicity.
Chemotherapy teaching points university of florida. Nephrotoxicity was induced by a single intraperitoneal administration of cisplatin 6 mgkg in wistar rats. Neurologic evaluations should be performed regularly. The laboratory observation that forced hydration and diuresis may prevent nephrotoxicity facilitated the subsequent clinical development of cisplatin. Hyperbilirubinemias protective effect against cisplatin. Nephrotoxicity as a cause of acute kidney injury in children. Developing a more clinicallyrelevant mouse model of cisplatin nephrotoxicity cierra n. Toxicity induced by cisplatin based therapeutic regimens include gastrointestinal toxicity, myelotoxicity, neurotoxicity, ototoxicity and nephrotoxicity. Renal insufficiency can be prevented by hydration and forced disuresis. Pdf cisplatin has a wellestablished role in the treatment of broad. Cisplatin definition of cisplatin by medical dictionary. Note internal medicine palliative intravenous cisplatin treatment for concurrent peritoneal and pleural mesothelioma in a dog kyoungwon seo1, ulsoo choi2, yunchan jung1, suji hong1, yeeun byeun4, minsoo kang3, b. A known complication of cisplatin administration is acute kidney injury aki.
Nephrotoxicity induced by cancer chemotherapy with special. The disproportionate accumulation of cisplatin in kidney tissue contributes to cisplatininduced nephrotoxicity. Cspm2 hydration protocol for cisplatin chemotherapy. The purpose of this study was to compare severity and reversibility of renal damage in children after continuous and repetitive bolus administration of cisplatin and to correlate these data with pharmacokinetic parameters.
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