Posted by: Catherine Chaytor2 SEP 2020
As an oncology pharmacist and non-medical prescriber, I support patients through their systemic anti-cancer treatments (SACT), and the supportive treatments that can be given alongside to prevent side effects or, at the very least, reduce them to a tolerable level.
Some patients, inevitably, will not tolerate a specific regimen as well as others. For example, in my breast cancer clinic, I could predict that an older lady with comorbidities will tolerate capecitabine less well — so I would expect the consultant to apply a dose reduction from their first cycle of chemotherapy.
We can make predictions, but we can be caught out. A young, fit lady may have an awful time in her first cycle of capecitabine given at full dose, which could lead to a hospital admission for diarrhoea, neutropenia or even sepsis. A delay to cycle two, dose reduction and good supportive medication will hopefully get her back and stabilised on treatment.
But there’s a new field that can help us more accurately identify which patients are at risk of side effects to their chemotherapy: pharmacogenomics. We can look at the mutations in a person’s inherited DNA that predispose them to severe side effects to a particular drug.
And I have been putting this idea into action at Oxford University Hospitals NHS Foundation Trust, where I’ve led the implementation and running of a pharmacogenomics test for the DPYD gene.
The DPYD gene codes for the enzyme dihydropyrimidine dehydrogenase (DPD), which is critical in the breakdown of the chemotherapy drug 5-fluorouracil (5FU) and its prodrug capecitabine. Patients with specific mutations in the DPYD gene express less of the enzyme, resulting in accumulation of chemotherapy in the body; this causes severe side effects and, in some cases, death. Up to 8% of the population has a partial DPD deficiency. A critical DPD deficiency is strongly correlated with death from capecitabine toxicity.
NHS England does not currently commission DPYD testing, but we put a business case forward to fund the testing internally within the trust. We agreed to a two-year pilot, which began in June 2019, to DPYD test all patients before starting 5FU or capecitabine-based regimens, and to research around the health and economic value that the testing could provide.
During our usual care, our cancer pharmacists have been used to checking pathology reports and validating chemotherapy regimens to ensure the best treatment, and our pharmacists second-check our doctors’ treatment selections.
But our testing put pharmacists at the forefront of pharmacogenomics. The people at ToxNav, who make the test that we are using, said that they have never had pharmacists lead or run the process like we do. Pharmacists are experts in medicines safety and effectiveness, so putting them at the heart of the process was a logical step; SACT prescriptions cannot be released without validation by a cancer pharmacist.
We were daunted by rolling out DPYD testing across all of oncology at our busy cancer centre. Around 600 patients are started on eligible regimens each year, and we did not want to add extra steps to the patient’s journey that could lead to delays or add further workload to the medical teams.
So we put a standard operating procedure in place where the doctor agrees to the patient having the DPYD test at the point of referral for chemotherapy. The doctor then proceeds to prescribe the chemotherapy at the normal starting dose for the patient’s demographics, with the knowledge and confidence that the cancer pharmacists will interpret the results of the DPYD assay when the result is available, and alert them if there is a problem.
The result is received within two weeks, which is our usual wait time for starting routine chemotherapy. The cancer pharmacists will not validate or release the prescription without reviewing and interpreting the DPYD assay result, and patients are contacted only if there is an issue.
Objectively, the clinical teams are reporting a drop in the number of admissions owing to severe toxicity to 5FU and capecitabine, and there have been no reported deaths with DPD deficiency as a causative factor since the testing was rolled out.
The true health and economic value of the test will be evident only after we can intepret our first year of data.
We hope the outcome of the pilot will inform commissioners, both locally and nationally, on whether to continue to offer DPYD testing in routine practice within the NHS, which we predict will save lives.
As we move further into the age of personalised medicine, we’ve shown that pharmacists can be leaders, and not just verifiers, in pharmacogenomics.
Catherine Chaytor is senior cancer pharmacist and lead for oncology at Oxford University Hospitals NHS Foundation Trust