Side Effects and New CDK Inhibitor Class of Breast Cancer Drugs
by C.H. Weaver M.D. 10/2020
According to a report published in The Oncologist, cyclin-dependent kinase (CDK) inhibitors, a new class of oral drugs for treating breast cancer, appear to be very well tolerated with minimal side effects.
Three CDK inhibitor drugs have now been approved by the Food and Drug Administration for the treatment of hormone receptor-positive (HR+) metastatic breast cancer.
A major hallmark of cancer cells is their ability to multiply rapidly; CDK inhibitors interfere with this process by blocking the activity of enzymes known as CDKs, particularly CDK 4 and CDK 6, that help to regulate cell division. For effectively treating breast cancer, CDK inhibitors are usually combined with endocrine therapy, which works by preventing hormones from binding with their respective receptors on the cancer cells.
CDK inhibitors will replace traditional endocrine therapies in many situations, and have a unique set of side effects. Therefore it is important to have an understanding of their side effects and drug interactions as they increasingly represent a therapeutic choice for selected patients with breast and other cancers.
The most common side effect is neutropenia, a low level of white blood cells, which can increase the chance of infection. Neutropenia is temporary and dose-dependent with the white blood count usually return to normal with dose-interruption or dose-reduction of the drug. Other side effects include diarrhea, fatigue, nausea, and alopecia (hair loss), which are usually mild and reversible by reducing the dose and taking regular breaks.
Patients and physicians should also be aware of certain drug-drug interactions with CDK 4/6 inhibitors, particularly for substances that inhibit the activity of an enzyme known as CYP3A, such as the antibiotic clarithromycin and grape juice. CYP3A is the prime enzyme responsible for breaking down CDK 4/6 inhibitors in the liver, and thus inhibiting its activity could lead to the build-up of high levels of the drug.
Beyond breast cancer CDK 4/6 inhibitors are being evaluated in lung, prostate, and ovarian cancer.