Palbociclib is a kinase inhibitor indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with:
- An aromatase inhibitor as initial endocrine based therapy in postmenopausal women; or
- Fulvestrant in women with disease progression following endocrine therapy.
Treatment of breast cancer cell lines with the combination of palbociclib and antiestrogens leads to decreased retinoblastoma protein (Rb) phosphorylation resulting in reduced E2F expression and signaling and increased growth arrest compared to treatment with each drug alone. In vitro treatment of ER-positive breast cancer cell lines with the combination of palbociclib and antiestrogens leads to increased cell senescence, which was sustained for up to 6 days following drug removal. In vivo studies using a patient-derived ER-positive breast cancer xenograft model demonstrated that the combination of palbociclib and letrozole increased the inhibition of Rb phosphorylation, downstream signaling and tumor growth compared to each drug alone.
Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein.
Dosage & Administration
Palbociclib capsules are taken orally with food in combination with an aromatase inhibitor or fulvestrant.
- Recommended starting dose: 125 mg once daily taken with food for 21 days followed by 7 days off treatment.
- Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability.
CYP3A Inhibitors: Avoid concurrent use of Palbociclib with strong CYP3A inhibitors. If the strong inhibitor cannot be avoided, reduce the Palbociclib dose.
CYP3A Inducers: Avoid concurrent use of Palbociclib with strong CYP3A inducers.
CYP3A Substrates: The dose of sensitive CYP3A4 substrates with narrow therapeutic indices may need to be reduced when given concurrently with Palbociclib.
Most common adverse reactions (incidence ≥10%) were neutropenia, infections, leukopenia, fatigue, nausea, stomatitis, anemia, alopecia, diarrhea, thrombocytopenia, rash, vomiting, decreased appetite, asthenia, and pyrexia.
Pregnancy & Lactation
Lactation: Advise not to breastfeed
Precautions & Warnings
Neutropenia: Monitor complete blood count prior to start of Palbociclib therapy and at the beginning of each cycle, as well as on Day 15 of the first 2 cycles, and as clinically indicated.
Embryo-Fetal Toxicity: Palbociclib can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
Targeted Cancer Therapy
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