Loperamide plus budesonide reduces the rate of toxic effects associated with neratinib for patients with human epidermal growth factor receptor-2 positive (HER2+) breast cancer, according to the results of a trial presented at the 2016 San Antonio Breast Cancer Symposium (Dec 6-10).
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Neratinib is often given to patients with HER2+ breast cancer as an adjuvant therapy after a year of trastuzumab treatment. The drug has been shown to be effective but is associated with heightened toxicity, often leading to more frequent episodes of grade 3 diarrhea.
In the phase II CONTROL trial, researchers led by Carlos H Barcenas, MD, MSc, Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, attempted to control the diarrhea events by giving prophylactic treatment with loperamide. Researchers created two cohorts, one with regimented loperamide doses and the other with loperamide in combination with budesonide, an anti-inflammatory drug.
Results of the study showed a reduction of grade 3 diarrhea in the cohort with regimented loperamide to approximately 25% and a reduction in the cohort with loperamide and budesonide to approximately 15%. The combination was thus deemed more effective, although it also increased rates of constipation, nausea, and fatigue.
The researchers said they are intent on lowering the rate of grade 3 diarrhea even farther. “[Fifteen percent is] actually a good number, but the idea is to try to decrease it even more. Of course, the mechanism of action of the diarrhea, although we think it’s inflammatory, there may be other factorials, so the idea is to use other agents,” said Dr Barcenas in an interview with OncLive.
The next agent researchers will be testing is colestipol, an acid bile sequestrant, which has shown positive results in a metastatic setting. Colestipol will have its own cohort in further trials.
Researchers are also weighing other options, such as decreasing the dose of loperamide or giving budesonide as a single agent and using loperamide on an as-needed basis.
