Dana-Farber initiative will require pre-emptive genetic testing before 5-FU and/or capecitabine

Under a new Dana-Farber initiative, patients due to receive either of two commonly used chemotherapy drugs for the first time are being advised to take a pre-emptive genetic test to determine if they are at unusually high risk of severe side effects. Starting at the end of last year, the electronic health system alerts providers if a patient is planned to receive a chemotherapy regimen that includes 5-FU and/or capecitabine for the first time. The drugs are widely used in treatment of gastrointestinal and breast cancers. The blood test, which returns results in five to seven days, is not mandatory, but is highly recommended in the new Dana-Farber-wide initiative. The test can detect an uncommon genetic deficiency of an enzyme, DPD, which the body needs to process the chemotherapy drugs safely. A shortage or absence of the enzyme causes the drugs to rapidly accumulate in the body, causing side effects such painful lip, mouth and throat sores, intense diarrhea, weight loss, and fatigue. An estimated 1 to 8% of the population, depending on their ancestry, carry an inherited variation or defect in one copy of the DPYD gene, which directs the body to produce the DPD enzyme. A defect in one copy increases their risk of painful side effects putting them at high risk for dangerous side effects from 5-FU or capecitabine. Moreover, about one in 1,000 people have defects in both copies of their DPYD gene. These individuals are at high risk of extremely severe and potentially lethal side effects. “Even if patients don’t die, there’s still a significant risk of severe, non-fatal toxicities in carrier of deleterious DPYD gene variants,” says Douglas Rubinson, MD, PhD, a senior physician in the Gastrointestinal Center at Dana-Farber and a vocal advocate of gene testing for the condition. Patients found to have a partial deficiency of the DPD enzyme could be managed by starting with a 50% dose reduction of the drug, which can be increased up to the full dose over the first few doses if the patient tolerates it without unusually toxic effects, says Rubinson. But if the test reveals defects in both copies of the DPYD gene, “you can’t use 5-FU or capecitabine at all,” he says. “You have to find a regimen that doesn’t include those therapies.” The Dana-Farber screening program was initiated by Joseph Jacobson, MD, a senior physician and the former chief quality officer for the Institute, in consultation with other physicians and stakeholders within, and outside of, the Institute. Jacobson is co-chair of the working group on DPYD gene testing along with co-chair Andrew Wagner, MD, PhD, medical director of Adult Ambulatory Oncology. Angela Chen, PharmD, BCPS, regulatory compliance pharmacy specialist, and Samantha Morrison-Ma, MSN, MBA, program manager, Nursing Education, have taken the lead for pharmacy and nursing, respectively. Maria Ferzoco, of Quality and Patient Safety, is the project manager.