Palbociclib, sold under the brand name Ibrance, is a targeted therapy medication used for specific types of breast cancer that have spread to other parts of the body. It is designed to slow or stop the proliferation of cancer cells. This treatment is not traditional chemotherapy but belongs to a class of drugs that interfere with particular molecules involved in cancer growth.
Mechanism of Action
The growth and division of all cells are controlled by a sequence of events known as the cell cycle. In many cancers, this regulation is lost, leading to uncontrolled proliferation. Palbociclib works by targeting two proteins: cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6). These kinases act as accelerators for cell division, pushing the cell from a resting phase into active growth.
In certain breast cancer cells, the pathway involving CDK4 and CDK6 is overactive, causing the cells to divide relentlessly. Palbociclib functions as a selective inhibitor of CDK4 and CDK6. By binding to these kinases, the drug blocks their activity. This action prevents the phosphorylation of a protein called the retinoblastoma protein (Rb).
When the Rb protein is not phosphorylated, it remains active and halts the cell cycle in the first phase, known as G1. This G1 arrest prevents the cell from progressing to the S phase, where DNA replication occurs, stopping the cancer cells from multiplying. The effect is cytostatic, meaning it inhibits cell growth and division rather than directly killing the cells.
Patient Eligibility and Combination Therapy
Palbociclib is prescribed for individuals with advanced or metastatic breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). HR-positive means the cancer cells have receptors for hormones like estrogen or progesterone, which can fuel their growth. HER2-negative indicates the cancer cells do not have an excess of the HER2 protein. This HR+/HER2- subtype is the most common form of metastatic breast cancer.
The medication is administered in combination with endocrine (hormone) therapy. For post-menopausal women or men receiving their first hormone-based therapy for advanced disease, palbociclib is paired with an aromatase inhibitor, such as letrozole. Aromatase inhibitors work by reducing the amount of estrogen in the body, removing a growth signal for the cancer cells.
For patients whose disease has progressed after a previous round of endocrine therapy, palbociclib is combined with fulvestrant. Fulvestrant is a selective estrogen receptor degrader that blocks and damages estrogen receptors on cancer cells. While the endocrine therapy starves the cancer of hormonal growth signals, palbociclib simultaneously blocks the cell division machinery, creating a more robust suppression of the cancer.
Treatment Administration and Monitoring
Treatment with palbociclib is administered orally, allowing patients to take the medication at home. The standard dosage is a 125 mg pill taken once daily for 21 consecutive days, followed by a 7-day rest period, completing a 28-day treatment cycle. The capsules should be taken with food, while the tablets can be taken with or without food.
The 7-day break from treatment is an important part of the schedule. This rest period allows the body to recover, particularly the bone marrow, which can replenish blood cells. This helps manage some of the medication’s side effects before the next cycle begins.
Continuous monitoring is a standard part of the treatment process. Patients undergo regular blood tests, specifically complete blood counts (CBCs), to check their blood cell levels. These tests are required before starting treatment, at the beginning of each cycle, and on day 15 of the first two cycles. This frequent monitoring helps detect potential issues and allows for timely dose adjustments if necessary.
Common Side Effects
The most common adverse reaction is neutropenia, a significant decrease in the number of neutrophils, a type of white blood cell that fights infection. This condition can increase a person’s susceptibility to infections, which is why blood counts are monitored closely. Patients are advised to report any signs of infection, such as fever or chills, to their healthcare provider immediately.
Fatigue is another frequently reported side effect, with many patients feeling unusually tired or weak. Managing it often involves balancing rest with light activity. Nausea is also common, although it is typically mild to moderate and can often be managed with anti-nausea medications or dietary changes.
Other potential side effects include anemia (low red blood cell count), thrombocytopenia (low platelet count), mouth sores, and hair thinning. Gastrointestinal issues like diarrhea may also occur. It is important for patients to communicate any side effects to their medical team, as many can be effectively managed.