Effects of different doses of hyperbaric oxygen on cisplatininduced nephrotoxicity article pdf available in renal failure 293. Although recovery can occur after one episode of cisplatininduced aki, studies have indicated multiple episodes may lead to the. Dichloroacetate prevents cisplatininduced nephrotoxicity. Cell and biomarkerbased assays for predicting 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. Numerous studies have demonstrated that several mechanisms, including oxidative stress, dna damage, and inflammatory res ponses, are closely associated with cisplatininduced nephrotoxicity. You arrive, and the patient has stable vitals but is not responsive to pain. Acute kidney injury aki is a common clinical condition caused by loss of kidney function. 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.
Developing a more clinicallyrelevant mouse model of. Nephrotoxins are chemicals displaying nephrotoxicity. Platinum based anticancer drug candidate, with cisplatin, a. 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. Cisplatin is the generic name for the trade name drug platinol and platinolaq. A known complication of cisplatin administration is acute kidney injury aki. Implication for health policypracticeresearchmedical education. Chemotherapy teaching points university of florida. N14 received zinc sulfate plus cisplatin based regimen. Dogs receiving tavocept cisplatin and piroxicam had significantly lower nephrotoxicity grade than dogs receiving cisplatin and piroxicam without tavocept p 0. 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. 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.
Cspm2 hydration protocol for cisplatin chemotherapy. Pdf cisplatin has a wellestablished role in the treatment of broad. 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 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. 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. Cisplatin definition of cisplatin by medical dictionary. Combining cisplatin with cationized catalase decreases.
Cisplatin 1 mgml sterile concentrate summary of product. Numerous compounds have been studied to prevent cisplatin nephrotoxicity but only amifostine is us food and drug ad ministration fda approved for. You are paged because your patient is unresponsive. Reactive nitrogen species have also been studied in cisplatininduced nephrotoxicity.
Toxicity induced by cisplatin based therapeutic regimens include gastrointestinal toxicity, myelotoxicity, neurotoxicity, ototoxicity and nephrotoxicity. Research article effect of zinc sulfate in protection against. Cisplatin nephrotoxicity in children after continuous 72h. However, side effects in normal tissues and organs, notably nephrotoxicity in the kidneys, limit the use of cisplatin and related platinumbased therapeutics. To determine the incidence and evaluate the risk factors of. Palliative intravenous cisplatin treatment for concurrent. Predisposing factors such as age, pharmacogenetics, underlying disease, the dosage of the toxin, and concomitant medication determine and influence the severity of nephrotoxic insult. Renal toxicity is a clinical problem that affects 28. 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. Druginduced aki, as observed during cisplatinbased anticancer therapy, is responsible for about 20% of renal failure cases. Cisplatin is an anticancer antineoplastic or cytotoxic chemotherapy drug. Cisplatin mediates its tumorcidal effects via a number of different cytotoxic mechanisms. Magnesium supplementation and high volume hydration reduce.
Neurologic evaluations should be performed regularly. Developing a more clinicallyrelevant mouse model of cisplatin nephrotoxicity cierra n. See chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency. Nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. 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. Potential of pure phytoconstituents and herbs in protection. Education, science, technology and mathematics, university of canberra, australian capital territory. Jul 17, 2019 commonly reported side effects of cisplatin include. Intravenous route powder for solution administer under the supervision of a. Cisplatin nephrotoxicity can present in a number of ways including hypomagnesaemia, increased serum creatinine and urea. A 58yearold man with metastatic bladder cancer was treated with cisplatin, 70 mgm 2 body surface area, intravenously, after hydration with normal saline, 0. Clinical evaluation of tavocept to decrease diuresis time and.
Cisplatin is important chemotherapeutic agents used to treat solid tumors. It has been shown that mice deficient in ggt were resistant to the nephrotoxic effects of cisplatin. More side effects increased nephrotoxicity change in the drug metabolism 4. Cisplatin dose adjustment in patients with renal impairment. To date, although the pathophysiological basis of cisplatin nephrotoxicity has. Your patient is receiving cisplatin and his iv fluids are d5. 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. We hypothesized that mg infusion combined with low volume hydration may not be. 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. This medicine may lower the ability of the bone marrow to make blood cells that the body needs. One of the limiting side effects of cisplatin use is nephrotoxicity. Less nephrotoxicity but antitumour activity comparable to that of cisplatin. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia.
Effect of the ethanolic extract of scoparia dulcis in. Cisplatin and magnesium affect the same sodium and water channels in the outer medulla. Nephrotoxicity with cisplatin and antihypertensive medications. Sharp april 25, 2016 cisplatin is a nephrotoxic chemotherapeutic that causes acute kidney injury aki in 30% of patients. 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. To view other topics, please sign in or purchase a subscription. Nephrotoxicity may also be referred to as renal toxicity.
May use concomitant amifostine to decrease 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. Research over the past 10 years has uncovered many of the cellular mechanisms which underlie cisplatininduced renal cell death. Cisplatin treatment often produces extensive gastrointestinal side effects, which might lead to more magnesium depletion through anorexia and diarrhea. The initial injury triggers a proliferative response in renal tubular cells, which in the. Nephrotoxicity hepatotoxicity pulmonary fibrosis lomustine altered glucose metabolism streptozocin common. Nauseavomiting, anorexia, impaired fertility myelosuppression is the most common dose limiting toxicity also renal toxicity delayed nadir. The renal content of peroxynitrite and nitric oxide is increased in cisplatintreated rats.
The area of most interest in regard to cisplatin nephrotoxicity is the s3 segment of the osompt. Pdf prevention of cisplatin nephrotoxicity researchgate. Cisplatininduced nephrotoxicity causes altered renal. 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. Little is known about the association be tween the rate of cisplatin administration and the severity of cisplatininduced renal damage in children. Pathophysiology of cisplatininduced acute kidney injury. However, the major doselimiting side effect of cisplatin is its nephrotoxicity badary et al. The laboratory observation that forced hydration and diuresis may prevent nephrotoxicity facilitated the subsequent clinical development of cisplatin.
To evaluate the nephroprotective potential of ethanolic extract of aerial parts of plant scoparia dulcis against cisplatin induced nephrotoxicity in wistar rats. Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. Although it is best known for dna damage, cisplatin also causes cytoplasmic organelle dysfunction particularly with the endoplasmic. Nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. 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. 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. Hyperbilirubinemias protective effect against cisplatin. Cisplatin should not be given more frequently than once every 34 weeks. A urine output of 100 mlhour or greater will tend to minimise cisplatin nephrotoxicity.
Mean baseline serum creatinine concentration and peak serum creatinine concentration were 0. Cisplatin treated homozygous gunn rats showed significantly decreased karyolysisapoptosisnecrosis than the heterozygous gunn rats and the wistar rats in the osompt fig. Evidence for nephrotoxicity prevention with cisplatin. In childhood aki, incidence, prevalence, and etiology are not well defined. T d i i h l l i d to date, it is the only platinum drug. Cisplatin is a platinum containing drug first approved as an antineoplastic agent in 1978. 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 induced by cancer chemotherapy with special. There are several case reports of adverse cardiac effects of cisplatin due to hydro electrolytic imbalances depleted mg levels owing to nephrotoxicity5. See full prescribing information for cisplatin injection. Nephroprotective potential of plant was tested at two different doses in curative. Evidence for interventions to prevent nephrotoxicity.
Mar 31, 2015 nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6. 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. Nephrotoxicity may occur in as many as 50% to 75% of patients receiving the drug, and is apparently due to renal tubular injury. The disproportionate accumulation of cisplatin in kidney tissue contributes to cisplatininduced nephrotoxicity. Lack of therapeutic options has contributed to high mortality rates in aki patients.
No significant difference in karyolysisapoptosisnecrosis between. The participation of other enzymes such as aminopeptidase n apn, renal. Recent reports have shown that cisplatin induces depletion of mg and that mg supplementation can reduce renal toxicity. Nephrotoxicity was induced by a single intraperitoneal administration of cisplatin 6 mgkg in wistar rats. 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. Recently, a liposomal formulation of cisplatin, lipoplatin, was developed to reduce systemic toxicity of cisplatin. Apr 21, 2015 acute kidney injury aki is a common clinical condition caused by loss of kidney function.
The protective effects of maltol on cisplatininduced nephrotoxicity. Clinical evaluation of tavocept to decrease diuresis time. Al moundhri ms, al kindi, m, al nabhani m, al bahrani b. The role of oxidantantioxidant systems in chronic nephrotoxicity is uncertain. Nephrotoxicity is cumulative and often doselimiting. Nephrotoxicity renal toxicity managing side effects.
It is used as an antineoplastic agent in the treatment of metastatic tumors of the testis. Nat2 polymorphism in omani gastric cancer patientsrisk predisposition and clinicopathological associations. 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. Metabolomics for the early detection of cisplatininduced. Nov 26, 2007 cisplatin is associated with adverse drug reactions including renal damage and gastrointestinal dysfunction mishima et al. Cisplatin, which is an inorganic molecule containing a platinum ion, is an antineoplastic agent that has been used to treat various solid tumors. Cisplatin side effects, dosage, interactions drugs. Patients with preexisting cisplatin induced peripheral neurotoxicity generally do not worsen during carboplatin therapy. 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. Prevention of cisplatininduced ototoxicity in children and. Prevention of cisplatininduced ototoxicity in children. Highlights of prescribing information these highlights do not include all the information needed to use cisplatin injection safely and effectively.
Nephrotoxicity due to a aminoglycosides b cyclophosphamide c cisplatin d radiocontrast e analgesic f amphotericin g crystal forming drug 6. Indianapolis, in, usa according to the manufacturers instruction. Nephrotoxicity as a cause of acute kidney injury in children. Nephrotoxicity is the doselimiting toxicity of cisplatin. 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. Overview of the pathophysiological events in cisplatin nephrotoxicity. Renal insufficiency can be prevented by hydration and forced disuresis.
Even though the establishment of cisplatininduced nephrotoxicity can be alleviated. Collectively, these changes lead to acute kidney injury aki 4. 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. Nephrotoxicity is seen in about 20% of patients and frequently limits the clinical use of cisplatin. Original article risk analysis for cisplatininduced. It remains an important and effective therapy in many forms of cancer today. 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. Cisplatin nephrotoxicity american journal of kidney diseases. Pachrin3, wanhee kim4, cheolyong hwang1, daeyong kim3, hwayoung youn1 and changwoo lee2 1departments of veterinary internal medicine. While toxicities include ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions 1,2, the main doselimiting side effect of cisplatin is nephrotoxicity 3,4,5.
Many different drugs and agents may cause nephrotoxic acute kidney injury aki in children. Cisplatin is a coordinate metal complex with significant antineoplastic activity and various adverse effects, including acute and chronic renal insufficiency and renal magnesium wasting. The nephrotoxic effect of cisplatin is cumulative and dosedependent and often necessitates dose reduction or withdrawal. Cisplatin is one of the most widely used and most potent chemotherapy drugs. Mitigation of acute kidney injury by cellcycle inhibitors. Exposure of tubular cells to cisplatin activates signaling pathways that are cell death promoting mapk, p53, ros, and so on or cytoprotective p21. The cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. However, its side effects include nephrotoxicity, neurotoxicity, bone marrow toxicity, gastrointestinal toxicity, and ototoxicity, which can limit its use. Cisplatin for injection, for intravenous use initial u.
Vip etoposideifoscisplatin, testicular chemoexperts. 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. 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. Additional studies with rats have shown that inhibition of ggt with acivicin protected them from cisplatin nephrotoxicity. 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. As a highly effective antineoplastic chemotherapeutic drug, cisplatin is widely used clinically to treat a variety of human malignancies. The role of oxidantantioxidant systems in chronic nephrotoxic ity is uncertain. Cisplatin enters renal cells by passive andor facilitated mechanisms. Lung cancer is a leading cause of cancer death in japan and other developed countries. Cisplatin induced nephrotoxicity an assessment based on. See below for a comprehensive list of adverse effects. 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.
Cellular toxicity cisplatin cisdiamminedichloroplatinum ii cddp is a. Cisplatin dosing, indications, interactions, adverse. Cisplatininduced kidney dysfunction and perspectives on. Laboratory study lrnf effects of different doses of. Nephrotoxicity of cisplatin combination chemotherapy in. Nephrotoxicity of cancer treatment in children medscape. Druginduced aki, as observed during cisplatin based anticancer therapy, is responsible for about 20% of renal failure cases. Cisplatin induces magnesium depletion, and magnesium deficiency itself may enhance cisplatin nephrotoxicity. Renal and electrolyte disturbances associated with cisplatin. Each of the medications in vip is designed to slow the growth of and kill testicular cancer cells. 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. Aug 05, 2015 nephrotoxicity and agents responsible nephrotoxic injury is damage to one or both kidenys that result from exposure to a toxic substance. Anaesthetic implications of chemotherapy bja education. Recent research has shed significant new lights on the mechanism of cisplatin nephrotoxicity, especially on the signaling pathways leading to tubular cell death.
Nephrotoxicity is the main side effect of cisplatin. Cisplatin is a widely used and highly effective cancer chemotherapeutic agent. Click the orange links and well show you extra information. 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. Cisplatin nephrotoxicity nephrotoxicity was reported in the initial clinical trials of cisplatin chemotherapy. Cisplatin nephrotoxicity is clearly doserelated and used to be considered dose limiting.
Chemotherapy and kidney injury american society of. Renal toxicity can be minimized by high volume hydration with mannitol diuresis. N14 received zinc sulfate plus cisplatinbased regimen. Nephrotoxicity is the most wellknown and clinically important toxicity. Cisdichlorodiammine platinum ii, or cisplatin, has emerged as a principal chemotherapeutic agent in the treatment of otherwise resistant solid tumors and is. Cisplatin is a major antineo plastic drug for the treatment of solid tumors, but it has dosedependent renal toxicity. Pdf effects of different doses of hyperbaric oxygen on. Jan 17, 2014 background nephrotoxicity is the doselimiting side effect of cisplatin justifying the assessment of renal function for dose adjustment.
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