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A New Treatment for Metastatic Breast Cancer

Aschenbrenner, Diane S. MS, RN

AJN The American Journal of Nursing: June 2015 - Volume 115 - Issue 6 - p 23,24
doi: 10.1097/01.NAJ.0000466315.46508.49
Drug Watch
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  • A new treatment is now available for postmenopausal women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer. Palbociclib (Ibrance) inhibits cyclin-dependent kinases 4 and 6.

Diane S. Aschenbrenner was previously the course coordinator for undergraduate pharmacology at Johns Hopkins University School of Nursing in Baltimore, MD. She currently teaches at Stevenson University in Stevenson, MD. She also coordinates Drug Watch:daschenbrenner@stevenson.edu.

Palbociclib (Ibrance) is a new oral medication approved for the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2–negative cancer. Palbociclib is used in combination with letrozole, an aromatase inhibitor approved for the treatment of postmenopausal breast cancer. Palbociclib was approved under the accelerated approval process.

Palbociclib inhibits cyclin-dependent kinases 4 and 6, which are molecules involved in the growth of cancer cells. Palbociclib blocks progression from the G1 phase of the cell cycle to the S phase, which reduces the proliferation of ER-positive breast cancer cell lines.

The most common adverse effects of palbociclib are myelosuppression (neutropenia, leukopenia, thrombocytopenia, or anemia), gastrointestinal effects (stomatitis, nausea, diarrhea, decreased appetite, or vomiting), upper respiratory infection, alopecia, fatigue, diminished strength, peripheral neuropathy, and nosebleeds. Infections secondary to neutropenia are possible. In one study, pulmonary embolism was reported at higher rates in patients taking palbociclib with letrozole than in those taking letrozole alone.

Palbociclib produces drug interactions through the cytochrome P-450 (CYP) enzyme system, specifically the isoenzyme CYP3A. Strong inhibitors of CYP3A should be avoided during therapy with palbociclib because they will significantly increase the circulating levels of palbociclib, increasing the risk of adverse effects. Strong inhibitors of CYP3A include grapefruit and grapefruit juice, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir–ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole. Strong or moderate inducers of CYP3A should also be avoided because they can decrease palbociclib plasma concentrations. Strong inducers of CYP3A include rifampin, phenytoin, carbamazepine, and St. John's wort. Moderate inducers of CYP3A include bosentan, efavirenz, etravirine, modafinil, and nafcillin. Dosages of some CYP3A4 substrates (drugs that are metabolized by CYP3A4) may need to be reduced if the drugs are taken concurrently with palbociclib. This is because the two drugs will compete to be metabolized by the same isoenzyme. If there isn't enough of the isoenzyme to fully metabolize both drugs, the metabolism of one or both can be impaired in an unpredictable fashion, creating elevations of drug serum levels. Drugs that have a narrow therapeutic index and are substrates of CYP3A4 (such as alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus) are likely to produce serious adverse effects if their serum level increases (hence the need for a lower dosage). Nurses should take a complete drug history to confirm that patients are not already taking prescribed or over-the-counter drugs or supplements that would cause an interaction with palbociclib.

Nurses should instruct patients to take palbociclib with food, which promotes absorption, and in combination with letrozole at approximately the same time every day. Palbociclib should be swallowed whole, without chewing or crushing. Patients shouldn't consume grapefruit or grapefruit products while taking palbociclib. If a patient vomits, she should not take an additional dose that day. If the patient misses a dose, she should not double it the next day. The palbociclib is taken for 21 days and then stopped for seven days to complete a 28-day cycle. The letrozole is taken daily for 28 days. Patients should be monitored for signs and symptoms of infections and pulmonary embolism.

Patient education should emphasize the major adverse effects: myelosuppression, infection, and pulmonary embolism. The nurse should ensure that the patient understands the importance of regular monitoring of neutrophil, red blood cell, and platelet levels. Nurses should provide patients with information on how to minimize their risk of infection through actions such as frequent handwashing, avoiding raw meat, and avoiding crowds.

Complete prescribing information is available at http://1.usa.gov/1IXunvv.

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