How is dosage of cancer therapy calculated for paediatric patients?

From Cancer Guidelines Wiki

Introduction

Calculating doses of cancer therapy in paediatric patients has many complexities compared to adults. The prescribing, supply and administration of cancer therapy in infants, children and adolescents should only be undertaken by specialist paediatric clinicians.

The pharmacokinetics of cytotoxic chemotherapy is different in paediatric patients compared to adults and it changes considerably from birth through to adulthood. The maturity of organ systems (particularly renal and hepatic) need to be considered when calculating doses of chemotherapy. Renal function can be difficult to assess in the younger paediatric patient.

Paediatric patients have a wide range of weights and heights making it more difficult to identify an erroneous value or a calculation error in an individual. It is difficult to immediately identify obesity in children based only on weight.

The usual processes for identification of medication errors (e.g. maximum dosing rules in electronic systems) may not alert the user if a dose error has occurred for a small child. Using body surface area dosing in patients with a weight <10kg can lead to significant overdoses of chemotherapy. The risk of errors in infants is increased 10-fold.

Protocols vary greatly for dose adjustments based on age/weight ranges. There is often limited information on appropriate dosing for new agents in the paediatric population.


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Evidence Summary

There is limited evidence to support detailed guidance on dosing of cancer therapy in children outside of specific protocols and individual clinical trials. The recommendations and practice points made here are based on consensus opinion and expert clinical experience.


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Recommendations

Consensus-based recommendationQuestion mark transparent.png

Patients who weigh more than 10kg should have cytotoxic chemotherapy dosed according to the BSA unless an approved protocol specifies otherwise. The Mosteller method is most commonly used (Mosteller, 1987).


Patients who weigh less than 10kg should have their cytotoxic chemotherapy dosed according to weight based calculations. The ‘rule of 30’ is used to adjust a chemotherapy dose from mg/m2 to mg/kg. This is where the mg/m2 dose is divided by 30 to get the mg/kg dose to administer (Ceja et al, 2013).


Paediatric patients should have their height and weight measured weekly when present in a health care facility and prior to the beginning of each cycle of treatment (Neuss et al, 2017; Belderson and Billett, 2017). Subsequent doses must be calculated on the new BSA or weight. If the dose has been prepared in advance with a previous height and weight, the dose administered must be within 5-10% of the dose according to the most recent height and weight.


Caution should be exercised when using a protocol where the study population did not include patients aged <1 year. Significant consideration of dose adjustments should be made by experienced clinicians before any doses are administered.


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Protocols vary in the age and weight cut-offs for weight based dosing in small children. Some protocols use age (e.g. <12 months or <3 years) whereas other protocols use weight (e.g. <10kg or <12kg) or BSA (e.g. <0.6m2). If a patient falls close to a category that may require a change in dose calculation there may be a significant increase in the calculated dose. It is recommended to closely review how the child has tolerated previous doses before giving the higher dose.


Protocols vary in how they cater for maturity of organ systems with respect to dosing of cytotoxic chemotherapy. Most protocols will have significant dose reductions for patients <6 months of age and modest dose reductions for patients between 6-12 months of age.


Carboplatin doses must be based on laboratory GFR results and not based on calculations using creatinine levels.


Renal function can be difficult to assess. GFR is the best indicator of renal function in children and adolescents. If a patient >1 year of age has a creatinine above that expected for their age, the Modified Schwartz formula should be used to estimate Creatinine Clearance (Schwartz and Work, 2009). Dose reductions or formal GFR measurement may be required.


Rounding of doses to allow safe measurement and administration is often required when tablets are the only available dosage form. This may mean the total weekly dosage is split over the week, potentially giving different doses on alternate days. The total weekly dose administered should be within 10% of the calculated dose based on the patient’s height and weight.

(Mosteller, 1987)[1] ;(Ceja et al, 2013)[2] ;(Neuss et al, 2017)[3] ;(Belderson and Billett, 2017)[4] ;(Schwartz and Work, 2009)[5]


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References

  1. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987 Oct 22;317(17):1098 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3657876.
  2. Ceja ME, Christensen AM and Yang SP. Dosing Considerations in Pediatric Oncology. US Pharmacist 2013;38, 8-11.
  3. Neuss MN, Gilmore TR, Belderson KM, Billett AL, Conti-Kalchik T, Harvet BE, et al. 2016 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards, Including Standards for Pediatric Oncology. Oncol Nurs Forum 2017 Jan 6;44(1):31-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28067033.
  4. Belderson KM, Billett AL. Chemotherapy safety standards: A pediatric perspective. Pediatr Blood Cancer 2017 Jun;64(6) Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28306217.
  5. Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 2009 Nov;4(11):1832-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19820136.

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