About 50%–68% of patients who take capecitabine develop HFS. Capecitabine is a prodrug of fluorouracil and is used to treat many cancers, including colorectal, gastric, and breast cancers 5, 6, 7, 8.
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HFS frequently occurs on the palms and soles of the feet and starts with minor skin changes such as erythema and edema, and then, if severe, proceeds to painful edema, blisters, and fissures.
Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of antineoplastic drugs such as pyrimidine analogs (e.g., capecitabine), kinase inhibitors, and pegylated liposomal doxorubicin 1, 2, 3, 4. Our results suggest that omeprazole may be a potential prophylactic agent for capecitabine-induced HFS. Moreover, based on the clinical database analysis of the Food and Drug Administration Adverse Event Reporting System, the group that has used any PPIs had a lower reporting rate of capecitabine-related PPE than the group that has not used any PPIs. Co-administration of omeprazole (20 mg/kg, p.o., at the same schedule) significantly inhibited these changes induced by capecitabine. Repeated administration of capecitabine (200 mg/kg, p.o., five times a week for 3 weeks) increased fluid content, redness, and tumor necrosis factor (TNF)-α substance of the mice hind paw. In this study, we investigated the ameliorative effects of omeprazole, a PPI on capecitabine-related HFS in mice model, and a real-world database.
Proton pump inhibitors (PPIs) have been reported to have anti-inflammatory effects. Although the pathogenesis of HFS remains unknown, some studies suggested a potential involvement of inflammation in its pathogenesis. Hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia (PPE), is a major side effect of capecitabine.
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