Regional cooling involves the application of ice packs to the wrists and ankles during chemotherapy infusion. As with cryotherapy, cooling is theorized to cause vasoconstriction and decreased circulation of the chemotherapeutic drug in the regional area, less extravasation into surrounding tissue, and a resulting reduction in cutaneous toxicity. Regional cooling has been evaluated in patients with cancer for the prevention of palmar-plantar erythrodysesthesia (PPE), a skin effect. Cryotherapy, based on the same theory, has been used for the prevention of mucositis.