Prescribing oral chemotherapy

The use of oral anticancer agents for the treatment of common malignancies has increased over the past few years. Of about 300 new anticancer agents in development, 20-25% are oral products.1 Many novel “target agents” such as inhibitors of the epidermal growth factor receptor (for example, erlotinib) and the vascular endothelial growth factor receptors (for example, sunitinib and sorafenib) are given orally. Patients prefer oral agents because they are more convenient, allow greater autonomy, and avoid venepuncture and the associated risks of indwelling venous catheters.2

Despite the advantages of oral anticancer agents, they do pose challenges such as poor compliance, a small but definite risk of unintentional overdose, and a greater risk of drug-drug and drug-food interactions.3 In this week's BMJ, Weingart and colleagues evaluate the safety practices of 62 National Cancer Institute designated centres in the United States with regard to prescribing oral chemotherapy.4 Such institutions would be expected to have high safety standards, but the survey found that few of the safeguards suggested for parenteral anticancer drugs were used for oral agents given in an ambulatory setting. More than half of the responding centres (23 of 42) had no required element for oral chemotherapy prescriptions; these included the diagnosis, protocol number, cycle number on the prescription, or a double check of the prescription by a second clinician.4

Since 1996, most US hospitals have devised programmes for the safe delivery of oral and parenteral chemotherapy.5 Recommendations emphasise the need for a comprehensive, interdisciplinary approach to reduce the number of errors whereby the accuracy of chemotherapy prescriptions must be verified by a system of double checking.67 Weingart and colleagues' survey suggests that these safety recommendations often assume chemotherapy agents will be administered in a monitored, clinical environment, and not in an ambulatory setting. Oral anticancer agents given outside a healthcare centre require the same safeguards as parenteral agents, unless the dosing regimen of oral agents can be simplified.

One source of prescribing error stems from the unique practice in oncology of calculating doses on the basis of the patient's body surface area (calculated from height and weight). This practice has been repeatedly questioned in recent years, and the evidence to support it is limited.8910

The rationale for using body surface area to calculate drug doses is even less clear for oral agents than for parenteral ones, as pharmacokinetic variability between patients is greater for oral agents and less likely to be associated with body size.1112 Thus, calculating the dose of oral anticancer agents on this basis is unlikely to improve safety and may even increase the risk of underdosage or overdosage. Some drug companies have responded to these risks by creating standard starting doses for all patients. However, some widely used oral agents (such as capecitabine) still require dosing on the basis of body surface area.13

For doses based on body surface area, safety standards should be the same as for parenteral therapy—the prescription should include the patient's height, weight, and body surface area; dose per body surface area; final calculated dose; and total number of doses per treatment course. Dosing calculations should be verified by a multidisciplinary system of double checking.678

Prescriptions for agents with standardised dosing may not need these elaborate safety measures as the risks of the prescriber making a dosing error or the patient making an error when taking the drug are much lower.

The use of oral anticancer agents will continue to increase as more agents come on to the market. We suggest standardising oral anticancer doses in an effort to eliminate unnecessary dosing complexity and thereby improve patient safety.