Influence of co-morbidity on renal function assessment by Cockcroft-Gault calculation in lung cancer and mesothelioma patients receiving platinum-based chemotherapy

Our plain-English summary of Influence of co-morbidity on renal function assessment by Cockcroft-Gault calculation in lung cancer and mesothelioma patients receiving platinum-based chemotherapy, by R.A. Hubner, R. Goldstein, S. Mitchell, et al (Lung Cancer, 2011).

The study

• Authors: R.A. Hubner, R. Goldstein, S. Mitchell, A. Jones, S. Ashley, M.E. O'Brien, S. Popat
• Journal: Lung Cancer
• Published: 2011;73(3):356-60
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Creatinine clearance (CrCl) estimation by Cockcroft-Gault calculation (CG) often replaces measurement of glomerular filtration rate (GFR) by [(51)Cr]-ethylenediaminetetraacetic acid clearance (EDTA). Co-morbidity, age, and renal impairment influence the accuracy of CG, whilst the relationship between CG and EDTA has been poorly assessed in lung cancer patients, a population significantly affected by these covariates.

Methods: Retrospective analysis of co-morbidity, nephrotoxic drug use, chemotherapy toxicity, and correlation between paired CG and EDTA, in 388 lung cancer and mesothelioma patients receiving platinum-based chemotherapy.

Results: Potentially nephrotoxic co-morbidity or medication use occurred in 47% of patients, and was twice as likely in those aged >70 years (OR=2.07; 95%CI: 1.25-3.44, p=0.003). Patients with co-morbidity or nephrotoxic medication use had a lower EDTA compared to those without these baseline factors (p=0.02), but were not significantly more likely to experience chemotherapy toxicity. CG and EDTA correlation was high (r(2)=0.68), but reduced in patients with ETDA<50 ml/min (r(2)=0.26, p=0.02) or >120 ml/min (r(2)=0.32, p=0.09), and in those with CG>120 ml/min (r(2)=0.20, p=0.01). The correlation between CG and EDTA was not significantly altered in patients with co-morbidity or nephrotoxic medication use. CG bias (mean percentage error) and precision (mean absolute percentage error, MAPE) were 7% and 26%, respectively, and precision was impaired in patients with abnormally raised serum creatinine (MAPE 65%, p<0.0001).

Conclusion: CG estimation of CrCl is accurate and safe in lung cancer patients with potentially nephrotoxic co-morbidity or concomitant medication, but should not be used when values are outside the range 50-120 ml/min, or with abnormally elevated serum creatinine.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

In plain English

This retrospective study looked at 388 patients given platinum-based chemotherapy at the Royal Marsden Hospital, London, from November 2007 to April 2009. Most had lung cancer or mesothelioma (66 had mesothelioma); 8 had thymoma and 1 carcinoid. It did not study asbestos exposure. The authors compared a Cockcroft-Gault kidney-function estimate, calculated from blood creatinine, with direct EDTA measurement in the 250 patients who had both. Nearly half had illnesses or medicines that could affect the kidneys, more often those over 70 (odds ratio 2.07, 95% confidence interval 1.25 to 3.44). The two methods were highly correlated overall (r2 = 0.68), and such illnesses or medicines did not significantly change this. Correlation was weaker with measured function below 50 ml/min (r2 = 0.26) or estimates above 120 ml/min (r2 = 0.20). The formula overestimated by 7% on average. Its average error regardless of direction was 26%, rising to 65% with serum creatinine at or above the upper limit of normal. The authors concluded the formula is safe in most lung cancer patients. They advised caution, and direct measurement, outside 50 to 120 ml/min or with abnormally raised creatinine.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective analysis of hospital records comparing a calculated estimate of kidney function (Cockcroft-Gault) with a measured value (51Cr-EDTA clearance)
• Who was studied: 388 patients treated with platinum chemotherapy in the Lung Unit of the Royal Marsden Hospital, London, from 1 November 2007 to 30 April 2009. Diagnoses were 235 non-small cell lung cancer, 78 small cell lung cancer, 66 mesothelioma, 8 thymoma and 1 carcinoid. Both kidney-function values were available for 250 patients.
• Exposure: Not an asbestos exposure study. The factors examined were carboplatin- or cisplatin-containing chemotherapy (244 carboplatin, 144 cisplatin), kidney-related co-morbidity, and potentially nephrotoxic medication.
• Main results:
  • Among all 388 patients, 47% had potentially nephrotoxic co-morbidity or medication use. These factors were more likely in patients over 70 (n = 92) than in those aged 70 or under (OR = 2.07; 95% CI 1.25 to 3.44, p = 0.003).
  • 30% of patients had chemotherapy toxicity, defined as a dose reduction, a switch from cisplatin to carboplatin, or stopping treatment. Co-morbidity or nephrotoxic medication use did not significantly influence the likelihood of toxicity.
  • In the 250 patients with both values, overall correlation between the estimate and the measurement was high (r2 = 0.68). Correlation was reduced in patients with EDTA below 50 ml/min (r2 = 0.26, p = 0.02), above 120 ml/min (r2 = 0.32, p = 0.09), and with CG above 120 ml/min (r2 = 0.20, p = 0.01).
  • The correlation between the estimate and the measurement was not significantly altered in patients with co-morbidity or medication use potentially associated with kidney impairment.
  • On average the formula overestimated kidney function (mean percentage error +7%). Mean absolute percentage error was 26% overall, 76% in patients with EDTA below 50 ml/min, and 65% in patients with serum creatinine at or above the upper limit of normal.
  • Of 147 patients whose carboplatin dose was first calculated from the formula, 32 (22%) had their dose changed once an EDTA result became available: an increase in 10 and a reduction in 22.
• The authors' conclusion: The authors concluded that the Cockcroft-Gault estimate is safe in most lung cancer patients. They said it should be used with caution when values are outside 50 to 120 ml/min or serum creatinine is abnormally raised, and they recommended EDTA measurement in those cases.
• Limitations the authors state:
  • Clinical data were collected retrospectively, especially the data on chemotherapy toxicity.
  • Estimate or measurement values were missing for some patients, although the authors judged this unlikely to cause systematic bias.
  • No data were collected on tumour response or survival.
  • Other estimating formulas (Wright, Jelliffe, MDRD) were not assessed.
  • The study's power to detect differences in correlation was smaller when patient groups were of uneven size.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Mesothelioma, Chemotherapy.

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