Oncology

Pharmacogenetics in Oncology – Precision Cancer Management

As an oncologist, you may frequently find yourself challenged by patients with multiple health issues already taking several medications by the time they’re referred to your practice. Our partners at YouScript can help you chart a safer, more effective course with additional medications.

Say you see a patient for evaluation of possible lung cancer. When you perform a physical and take a history, the patient relates a background of sensitivity to medicines, but can’t tell you exactly what that sensitivity entails. That can make adjusting or prescribing other drugs difficult, complicated by the fact there are more than 20 oncology medicines with pharmacogenetics listed on the FDA label. A growing number of these have warnings about genetics altering patient response.

How do you make the best treatment choice for your patient?

In the past, oncologists had little choice but to try medications without knowing in advance how such patients might genetically respond. But no more: with precision prescribing by YouScript, you can know upfront what medications will likely prove the most effective for your patient – and which ones will not. And you’ll know precisely which medications will interact with the prescriptions and supplements your patient is already taking.

YouScript Helps You Achieve Optimal Prescribing

Many opioids, antiemetics, and antidepressants that are used alongside chemotherapy are metabolized by CYP2D6 and CYP2C19, and as the table below demonstrates, variations are extremely common. This genetic variability is often the most important consideration governing how an individual patient will respond to medicines.

YouScript includes testing of all clinically significant genetic variants in CYP2D6, CYP2C9 (including VKORC1), CYP2C19, CYP3A4 and CYP3A5 enzymes responsible for metabolizing the majority of medications.

In this case, after testing, the YouScript Precision Prescribing Report states that your patient is a CYP2D6 Intermediate Metabolizer, CYP2C9 poor metabolizer with VKORC1 high sensitivity, CYP2C19 normal metabolizer, CYP3A4 normal metabolizer and CYP3A5 normal metabolizer.As the tabels below demonstrate, many of your other patients may also have cytochrome variability.

The Majority of Patients Have Cytochrome P450 (CYP) Variability

GenePoor MetabolizerIntermediate MetabolizerNormal MetabolizerRapid or Ultra Rapid Metabolizer
CYP2D610%35%48%7%
CYP2C92-4%>35%~60%N/A
CYP2C19*2-20%24-36%14-44%30%

*CYP2C19 variability depends on ethnicity.

Ethnicity
Gene   Variant ActivityCaucasian     Asian  African
CYP3A4Decreased5.3%0%0%
CYP3A5Decreased93%75%27-50%

 

Other tests Genelex offers that analyze variations in non-CYP genes that metabolize specific chemotherapy medications include:

TPMT – azathioprine (Imuran), mercaptopurine (Purixan), thioguanine (Lanvis)

DPYD – capecitabine (Xeloda), 5-fluorouracil (Adrucil)

The YouScript Precision Prescribing Report also gives you secure web access to the patient’s cytochrome results. A comprehensive drug-gene database is at your fingertips making it easy to quickly add your patient’s medication list and identify an interaction. For example, you prescribe tamoxifen for adjuvant breast cancer.

After a long battle with breast cancer, your patient begins to complain of depression, so you consider therapy with an antidepressant. After adding fluoxetine to the patient’s YouScript profile, you notice an interaction warning next to tamoxifen. The patient’s CYP2D6 intermediate matabolizer phenotype an inhibition by fluoxetine causes a decrease in the levels of tamoxifen’s active metabolite.

YouScript Helps You with Polypharmacy Safety – Now and in the Future

Like this patient, many oncology patients are also battling other conditions such as heart disease, pain, or psychiatric conditions that make multiple prescriptions necessary. Our body’s limited capacity to process medications is easily slowed by competition between drugs, supplements and over-the-counter medication. This is further compromised in patients with genetic variations.

Whether a patient is genetically a poor metabolizer or has become a poor metabolizer because of other medications, it’s been shown by prospective trials, population analyses, and case studies he or she can experience an increase in adverse drug events because of reduced elimination.

The clinical note in YouScript states to avoid concomitant use of luoxetine and tamoxifen and consider switching to an aromatase inhibitor in postmenopausal women that are CYP2D6 intermediate metabolizers. You’ll notice an alternative button next to tamoxifen. When you click on it, it will list medications other medications for treating breast cancer that are not as reliant on the CYP2D6 pathway. If you select anastrozole instead, you’ll note that there are no longer any new significant interaction warnings.

YouScript is Updated with the Latest Clinical Knowledge on Drug Metabolism

To further complicate the matter, the body of knowledge on drug metabolism is constantly growing. Numerous clinical studies continue to be published on both drug metabolism and drug-gene interactions. Even the most committed physician cannot keep up with this constantly growing body of knowledge.

YouScript saves you time. Our team of pharmacists and physicians has done the research on drug metabolism and drug and gene interactions for you. YouScript is updated multiple times each month with the latest clinical information.

After navigating the YouScript analytics software for your first patient and discovering how helpful it is in choosing safe and effective medications, you may well find that YouScript helps you treat other patients.

Which Patients Benefit Most from DNA sensitivity testing?

DNA sensitivity testing has significant impact for many patients, including those:

  • Taking multiple medications
  • Prescribed any of the more than 100 FDA-approved drugs with pharmacogenetic information in their labels, including the following:
    • Plavix® (clopidogrel)
    • Coumadin® (warfarin)
    • Strattera® (atomoxetine)
    • Abilify® (aripiprazole)
    • Lopressor® / Toprol® (metoprolol)
    • Clozaril® (clozapine)
  • Who complain their medications are not working
  • Wary of standard dosing based on prior negative experiences
  • On complex drug treatment plans for cancer or HIV infection
DNA sensitivity testing is typically covered by most private insurers and Medicare in specific instances.

Call 800-TEST-DNA to ask how it works. There is no cost to you and supplies will be sent out immediately. Pharmacists and other support staff are there to help whenever you have questions

How to Integrate YouScript Into Your Practice

  1. Ask your YouScript consultant, call 800-TEST-DNA or sign up online.
  2. Receive your YouScript testing supplies.
  3. Collect a swab or blood sample from your patient and ship it in a prepaid mailer.
  4. Receive the Precision Prescribing Report with recommendations from a local YouScript network pharmacist.
  5. Counsel your patient on their YouScript results and adjust treatment plan as needed.
  6. Learn more about YouScript