Partial reversibility of cisplatin nephrotoxicity in children

Brock, Pénélope; Koliouskas, Dimitri E.; Barratt, T. M.; Yeomans, Elizabeth; Pritchard, Jon

doi:10.1016/s0022-3476(05)83372-4

Cited by 99 publications

(93 citation statements)

References 11 publications

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“…The results of this follow-up study confirm previous reports of the frequency, nature and severity of cisplatin-induced glomerular and proximal nephron nephrotoxicity in children, leading to clinically important reductions in GFR and serum magnesium concentration (Ettinger et al, 1981;Hayes et al, 1981;Womer et al, 1985;Goren et al, 1986;Sheldon et al, 1987;Bianchetti et al, 1990;Brock et al, 1991). These adverse effects occurred despite the use of hyperhydration protocols, which appear to reduce the frequency and severity of nephrotoxicity, rather than abolish it altogether (Daugaard and Abildgaard, 1989).…”

Section: Discussionsupporting

confidence: 86%

“…Despite numerous publications concerning cisplatin nephrotoxicity in adults, there is less information and no clear consensus on the importance of patient-and treatment-related risk factors for the development of nephrotoxicity in children. Furthermore, as there are few data concerning the long-term outcome of cisplatin nephrotoxicity in children (Brock et al, 1991), especially that of tubular toxicity, concern persists over the possibility that significant chronic renal damage may become evident only in adult life. Correspondence to: R Skinner Therefore, this study was designed to investigate these issues.…”

mentioning

confidence: 99%

“…Indeed, recent evidence has suggested that cisplatin may be more active than carboplatin in some germ cell tumours in adolescents and adults (Bajorin et al, 1993). However, even with the use of hyperhydration and other protective measures, nephrotoxicity is still a common and potentially serious adverse effect of cisplatin in both adults (Madias and Harrington, 1978;Schilsky et al, 1982;Daugaard and Abildgaard, 1989) and children (Womer et al, 1985;Brock et al, 1991). Despite numerous publications concerning cisplatin nephrotoxicity in adults, there is less information and no clear consensus on the importance of patient-and treatment-related risk factors for the development of nephrotoxicity in children.…”

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confidence: 99%

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Cisplatin dose rate as a risk factor for nephrotoxicity in children

Skinner

Pearson²,

English³

et al. 1998

Br J Cancer

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Summary The purpose of the study was to evaluate the incidence, risk factors and changes in severity with time of cisplatin nephrotoxicity in children. A total of 35 children underwent measurement of glomerular filtration rate (GFR) and tubular function after completion of cisplatin chemotherapy. No child received ifosfamide. A clinically relevant 'nephrotoxicity score' was derived from GFR and serum magnesium. Followup studies were performed in 16 children at 1 year and in 15 at 2 years after cisplatin. Considerable interpatient variability in nephrotoxicity was observed. Treatment was modified in three patients because of nephrotoxicity. GFR was low in 18 out of 31 patients. Proximal nephron toxicity caused hypomagnesaemia in ten patients and hypocalcaemia in five patients. Elevated urinary N-acetylglucosaminidase excretion was seen in 22 out of 30 children, indicating subclinical tubular toxicity. Nephrotoxicity was less severe in children who received cisplatin courses at a dose rate of 40 mg m-2 dar' than in those who received higher dose rates (P < 0.005), but there was no correlation with total dose received. Follow-up studies revealed partial recovery of GFR (P < 0.05). Glomerular and proximal nephron toxicity are common in children treated with cisplatin, and more severe at higher dose rates. Despite partial recovery of GFR, the long-term outcome of nephrotoxicity remains unknown and careful monitoring of chronic toxicity is necessary.Keywords: cisplatin; nephrotoxicity; children The use of combination chemotherapy has led to dramatic improvements in the survival rates from many childhood malignancies during the last three decades. However, cytotoxic drugs may also cause severe and chronic side-effects, leading to permanent ill-health, disability or even premature death (Morris Jones and Craft, 1990). The development of effective strategies to prevent these adverse events depends on careful evaluation of toxicity both during and after treatment.In view of its established efficacy, cisplatin has retained an important role in the treatment of several childhood solid tumours, including neuroblastoma, osteosarcoma, hepatic and brain tumours, despite the increasing use of its apparently less nephrotoxic analogue carboplatin. Indeed, recent evidence has suggested that cisplatin may be more active than carboplatin in some germ cell tumours in adolescents and adults (Bajorin et al, 1993). However, even with the use of hyperhydration and other protective measures, nephrotoxicity is still a common and potentially serious adverse effect of cisplatin in both adults (Madias and Harrington, 1978;Schilsky et al, 1982;Daugaard and Abildgaard, 1989) and children (Womer et al, 1985;Brock et al, 1991). Despite numerous publications concerning cisplatin nephrotoxicity in adults, there is less information and no clear consensus on the importance of patient-and treatment-related risk factors for the development of nephrotoxicity in children. Furthermore, as there are few data concerning the long-term outcome of cisplatin nep...

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Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Cisplatin dose rate as a risk factor for nephrotoxicity in children

Skinner

Pearson²,

English³

et al. 1998

Br J Cancer

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“…The incidence of hypomagnesemia increased with cumulative cisplatin ( Renal electrolyte disturbances frequently occur with platinum based chemotherapy despite corrective measures and as such should be regularly monitored in patients on chemotherapy. The apparent partial reversibility of glomerular but not tubular toxicity is consistent with the observation of Brock et al, 1991 and is an important finding in view of continued use of platinum coordination complexes in various combination chemotherapy protocols.…”

Section: Discussion:-supporting

confidence: 82%

Renal and Electrolyte Dysfunction Associated With Platinum Based Chemotherapy.

Mustafa¹,

Bhat²,

M.S.³

2017

IJAR

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Background:-Nephrotoxicity is dose limiting side effect of platinum coordination complexes( cisplatin, carboplatin and oxaliplatin) which have revolutionised the treatment of many human cancers. Objective:-To determine the renal and electrolyte abnormalities associated with platinum based chemotherapy. Methods:-70 newly diagnosed cancer patients who were put on combination chemotherapy were evaluated for various renal and electrolyte abnormalities during chemotherapy and were subsequently followed at six monthly intervals for a period of 18 months to ascertain any progression or reversibility in their renal functions. Results :-Among the 70 patients studied, 42 patients received a cisplatin based chemotherapy; 7 received carboplatin based chemotherapy and 21 received oxaliplatin based chemotherapy. Cisplatin was the most nephrotoxic among the three drugs and nephrotoxicity was cumulative. There was successive rise in serum creatinine from 0.68±0.15mg/dl to 1.14±0.53mg/dl and successive fall in creatine clearance from 98.9±15.6ml/min to 67.1±27.6 ml/min with each cycle of cisplatin. I6.7% patients developed azotemia(creat> 1.5mg/dl)after second cycle and 24.4% after third cycle of cisplatin. Nephrotoxicity was uncommon with carboplatin and oxaliplatin. There was persistence of deranged renal functions at followup even after stopping chemotherapy. Serum magnesium also fell sequentially from pre-treatment value of 0.9±0.2mg/dl to 0.61±0.17 mg/dl at sixth cycle. Hypomagnesia persisted in 23 of 35 patients at follow up. Hypokalemia occurred more frequently than hypocalcemia in cisplatin group. Electrolyte abnormalities were less common with carboplatin and oxaliplatin. Conclusions:-Cisplatin has cumulative nephrotoxicity which can persist even after the drug is stopped. Renal functions and electrolytes are to be closely and regularly monitored in patients on chemotherapy even when the drug has been stopped.

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“…Cases of atrial arrhythmia, supraventricular tachycardia, bradycardia, ST-T wave changes, left bundle branch block, acute ischemic events, myocardial infarction, myopathy have been reported during treatment with cisplatin [4,5]. Furthermore, cisplatin is one of the most frequently cytotoxic drugs associated with atrial fibrillation (AF) [6].…”

Section: Discussionmentioning

confidence: 99%

Recurrent Complete Atrioventricular Block During Cisplatin Infusion: A Case Report

Özcan¹,

Cirit²,

Kıykım³

2011

J Clinic Experiment Cardiol

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Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of malignancies. The clinical use of cisplatin is limited by its severe adverse effects. Acute or long term cardiotoxicity is the most important doselimiting toxicity of cisplatin Cases of angina, myocardial infarction, and atrial arrhythmia have been reported during continuous infusion of cisplatin, but atrioventricular block (AV) has not been reported. Herein, we report a case with recurrent AV block that developed during cisplatin infusion, for the first time.

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Partial reversibility of cisplatin nephrotoxicity in children

Cited by 99 publications

References 11 publications

Cisplatin dose rate as a risk factor for nephrotoxicity in children

Cisplatin dose rate as a risk factor for nephrotoxicity in children

Renal and Electrolyte Dysfunction Associated With Platinum Based Chemotherapy.

Recurrent Complete Atrioventricular Block During Cisplatin Infusion: A Case Report

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