The Truth Behind 'Chemo Overdosing'
- Doctors SurvivorNet spoke to say the number of patients who experience chemotherapy toxicity or a “chemo overdose” is rare, adding that it’s a bit overblown and oversimplified and requires greater understanding.
- Chemotherapy toxicity affects a very small number of patients who possess the dihydropyrimidine dehydrogenase (DPYD) gene mutation, which impacts how they metabolize certain chemotherapy drugs.
- If patients are carriers of the DPYD gene mutation, they are at increased risk of toxicity from cancer treatments that contain fluoropyrimidines, which may include chemotherapy drugs capecitabine, floxuridine, and fluorouracil.
- Genetic tests can be as simple as a saliva swab or blood sample. It helps your care team determine if you have a specific mutation and can influence the type of chemotherapy you receive — how much or none at all — and if you are a carrier of DPYD and at increased risk of toxicity.
- A group of healthcare professionals has been pushing the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) to amend their guidelines requiring patients receiving certain chemotherapies to undergo genetic testing to determine if they are carriers of DYPD gene deficiency and minimize toxicity risk.
“It’s a very broad statement and a bit of an oversimplification,” Dr. J. Kevin Hicks, Associate Member Attending Precision Medicine Clinical Service at Moffitt Cancer Center, tells SurvivorNet.
Read MoreUnderstanding Chemotherapy
Research published in JIMD Reports, an open-access journal on inherited metabolic disorders, notes that in severe cases, people with DPYD may experience seizures and cognitive impairment, among other noticeable symptoms.
“Genetic variations in DPYD have also emerged as predictive risk factors for severe toxicity in cancer patients treated with fluoropyrimidines,” the researchers said in the study.
The National Cancer Institute (NCI) describes fluoropyrimidines as “one of a group of substances used to treat cancer,” which may include capecitabine, floxuridine, and fluorouracil, which are all types of chemotherapy drugs.
“There are numerous chemotherapy agents that we don’t fully understand the genetic variants affecting toxicity for every agent. Also, other things like obesity can impact chemo toxicity,” Dr. Hicks said.
WATCH: Genetic Testing Can Empower You With Information
Dr. Hicks adds patients concerned about how they will react to certain chemotherapies should talk with their doctor and consider genetic testing to assess toxicity risk.
Genetic tests can be as simple as a saliva swab or blood sample. The results help your care team determine if you have a specific mutation that puts you at higher risk for cancer. The results help doctors tailor your treatment and are helpful for cancer patients.
On a related note, genetic counselors help patients better understand the results of genetic testing. If they’ve undergone genetic testing, patients should ask their care team for a counselor.
“At Moffitt, we do DPYD testing to determine if patients are at increased risk of toxicity. The test results can also determine whether the drug needs to be decreased (dose reduction) on that particular treatment. DPYD testing is also included in our clinical workflows. When test results come back, they rest in the patient’s health records so future treatments ordered will know if they will affect the patient at possible risk of toxicity,” Dr. Hicks explained.
Testing for the DPYD Gene Mutation
For years, many health experts have pushed for the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) to amend their guidelines for patients receiving chemotherapies like fluoropyrimidine to require genetic testing to determine if the patient has DYPD gene deficiency. They believe such a measure would offer added insight into the type of treatment and the appropriate dosage a patient needs, with advanced knowledge of any toxicity risks.
Last year, a group of researchers pushed for ASCO and NCCN to amend clinical guidelines supporting testing for DPYD genetic variants before fluoropyrimidine chemotherapy.
“A recent meta-analysis of 13,929 patients in 35 studies found that patients carrying DPYD*2A were much more likely to experience severe life-threatening toxicity from fluoropyrimidine therapy than those carrying only wild-type alleles (one or two alternative forms of a gene mutation),” researchers said in their report published in the Journal of Clinical Oncology.
The researchers acknowledge that DPYD genotyping may impose a small financial burden on patients, but they believe “avoiding severe toxicity in the small population of DPYD variant carriers” is worth it.
RELATED: How Can Genetic Testing Help Determine the Right Form of Mental Health Treatment?
More on Genetic Testing
Genetic testing helps assess your cancer risk. If you have close relatives who are diagnosed with cancer or are found to have a genetic predisposition to care, such as carrying the BRCA gene mutation, genetic testing may be worth it.
“If somebody in your family is found to have a genetic predisposition to cancer, whether it be breast cancer or any other type of cancer, the first step is to start testing relatives most closely related to you,” Rachel Webster, a genetic counselor at MD Anderson Cancer Center, told SurvivorNet in a previous conversation.
“Those relatives might be brothers, sisters, parents, children. Those first-degree relatives are the ones that are at the highest probability of having that same genetic predisposition,” she added.
WATCH: Is genetic testing right for me?
Although genetic testing has been around for many years, some misconceptions exist about it.
“Genetic testing does not tell you about your risk for cancer related to environmental risk factors, such as smoking, diet, and exercise,” Webster said. “Genetic testing tells you about inherited cancer risks that you might see from your family members.”
WATCH: Myth Busting: Misconceptions about genetic testing.
Results from genetic testing also remain confidential — this includes your health insurance company — so changes to your insurance coverage won’t be affected.
Understanding Genetic Testing Results
“If someone gets a genetic test result back, it’s really important for them to know what this is. (What does this) mean for them? Put it into context,” Dr. Elisa Port, a surgical oncologist at Mount Sinai, previously explained to SurvivorNet.
Genetic counselors help patients during this critical phase of understanding.
WATCH: Genetic Counselors Are Here to Help.
“What does it mean for their family members? For their relatives? Genetic counseling to follow up genetic testing is a really, really important part of the whole process and is not always available in the direct-to-consumer type avenue [such as 23AndMe].”
According to the U.S. Centers for Disease Control and Prevention (CDC), your doctor can refer you for genetic counseling based on your personal and family health history.
Learn more about SurvivorNet's rigorous medical review process.
