International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency

doi:10.1016/j.ejca.2006.11.004

European Journal of Cancer

Volume 43, Issue 1, January 2007, Pages 14-34

https://doi.org/10.1016/j.ejca.2006.11.004 Get rights and content

Abstract

A SIOG taskforce was formed to discuss best clinical practice for elderly cancer patients with renal insufficiency. This manuscript outlines recommended dosing adjustments for cancer drugs in this population according to renal function. Dosing adjustments have been made for drugs in current use which have recommendations in renal insufficiency and the elderly, focusing on drugs which are renally eliminated or are known to be nephrotoxic. Recommendations are based on pharmacokinetic and/or pharmacodynamic data where available. The taskforce recommend that before initiating therapy, some form of geriatric assessment should be conducted that includes evaluation of comorbidities and polypharmacy, hydration status and renal function (using available formulae). Within each drug class, it is sensible to use agents which are less likely to be influenced by renal clearance. Pharmacokinetic and pharmacodynamic data of anticancer agents in the elderly are needed in order to maximise efficacy whilst avoiding unacceptable toxicity.

Introduction

Physicians face a special challenge in providing effective cancer chemotherapy for elderly patients. The elderly comprise a rapidly increasing treatment population that have undergone and are undergoing physiological changes associated with ageing, including declining renal function and decreasing reserve in multiple organ systems, which predispose them to unpredictable toxicities of cancer drug treatment. In addition, comorbidities (particularly vascular pathologies) and associated polypharmacy complicate the situation still further. It has been reported that elderly cancer patients take a median of five different prescribed medications, while a quarter also use non-prescription drugs.¹ Polypharmacy can alter absorption by binding drugs in the gastrointestinal tract, changing adsorption or pH, and by competition for binding sites.

A SIOG taskforce discussed best clinical practice for treating elderly patients with renal insufficiency. This manuscript summarises the consensus recommendations of this taskforce with regards to dosing adjustments for cancer drugs administered to this population.

Section snippets

Renal insufficiency

The impact of physiological changes associated with age (for example modifications of renal function, hepatic metabolism, body fluids and muscle/fat repartition) on the pharmacokinetic and pharmacodynamic properties of drugs can be considerable, particularly for the renal elimination of drugs and metabolites. This is especially so for those drugs that are principally renally excreted and/or are nephrotoxic. These drugs typically have a narrow therapeutic range and for patients who present with

Age and age-related performance

For the elderly, there is a need to provide the best cancer treatment possible, whether curative or palliative, whilst avoiding the toxicities of cancer treatment that may be exacerbated by poor renal function or general functional status. Inadequate dosing may compromise efficacy whilst overestimation of renal function may impair safety. There is an ongoing belief that the elderly do not respond to standard treatment and/or cannot tolerate usual doses of cancer drugs. This is despite the fact

Renal function in the elderly

Renal function decline is common in the elderly. By the age of 70, renal function may have declined by 40%.⁹ This reduction in glomerular filtration rate (GFR) may lead to enhanced toxicity of drugs, particularly those with significant renal excretion, such as cisplatin, carboplatin, topotecan, methotrexate and ifosfamide. Damage to the vasculature or structures of the kidneys and haemolytic uremic syndrome (HUS) may also occur.¹⁰

The importance of the decline in GFR was first emphasised in a

Principles of dose adjustment

Patients with a degree of renal impairment are at risk of drug-induced renal toxicity and a higher total drug exposure and overall toxicity due to decreased renal excretion. Both parameters can have implications for drug selection and dosing. Overestimates of GFR in the elderly cancer patient can lead to serious errors in dosing¹² and subsequent deterioration of renal function. SIOG guidelines which discuss the measurement of renal function have also been developed.¹³ The nephrotoxicity of

Conclusions

Cancer treatment in the elderly is an individualised process that requires careful assessment of each patient prior to therapy initiation to achieve dose optimisation. Renal function should be assessed at least by calculation of CLcr in every patient, by aMDRD or Cockcroft-Gault formulae, even when serum creatinine is within the normal range.

Dose escalations can then be made at a later stage, if tolerability allows. Before initiating drug therapy, some sort of geriatric assessment should be

Conflict of interest statement

None declared.

Acknowledgements

An unrestricted educational grant was provided by Roche to support the SIOG task force activities. The authors would like to thank Gardiner-Caldwell US for their assistance in drafting the manuscript.

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Position PaperInternational Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency

Abstract

Introduction

Section snippets

Renal insufficiency

Age and age-related performance

Renal function in the elderly

Principles of dose adjustment

Conclusions

Conflict of interest statement

Acknowledgements

Ann Oncol

Am J Transplant

Eur J Cancer

Am J Kidney Dis

Cancer Treat Rev

Ann Emerg Med

Clin Geriatr Med

Ann Oncol

Semin Oncol

Ann Oncol

Semin Oncol

Gynecol Oncol

Rev Med Interne

Blood

Pathology

Gynecol Oncol

Kidney Int

Ann Oncol

Eur J Cancer

International Society for Geriatric Oncology (SIOG): a report from a SIOG task force on renal safety in the elderly

SIOG Newsletter

Incidence of renal insufficiency in cancer patients and evaluation of information available on the use of anticancer drugs in renally impaired patients

Med Sci Monit

A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients

N Engl J Med

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J Clin Oncol

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J Clin Oncol

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J Clin Oncol

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Cancer

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J Natl Cancer Inst

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J Clin Oncol

Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato) platinum in patients with impaired renal function

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Ann Intern Med

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Ann Intern Med

Prediction of creatinine clearance from serum creatinine

Nephron

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Br J Cancer

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Bull Cancer

Australasian Creatinine Consensus Working Group. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: a position statement. The Australasian Creatinine Consensus Working Group

Med J Aust

Multidimensional geriatric assessment reveals unknown medical problems in elderly cancer patients

J Clin Oncol

GPR® Anticancéreux. Guide de prescription des médicaments chez le patient insuffisant renal

Creatinine clearance as a predictor of ultrafilterable platinum disposition in cancer patients treated with cisplatin: relationship between peak ultrafilterable platinum plasma levels and nephrotoxicity

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Low urine osmolarity as a determinant of ciplatin-induced nephrotoxicity

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Position Paper
International Society of Geriatric Oncology (SIOG) recommendations for the adjustment of dosing in elderly cancer patients with renal insufficiency