low to stimulate additional clinical studies for the registration of intratumoral IL-2 therapy. United States Usually, in the U.S., the higher dosage option is used, affected by cancer type, response to treatment and general patient health. Patients are typically treated for five consecutive days, three times a day, for fifteen minutes. The following approximately 10 days help the patient to recover between treatments. IL-2 is delivered intravenously on an inpatient basis to enable proper monitoring of side effects. A lower dose regimen involves injection of IL-2 under the skin typically on an outpatient basis. It may alternatively be given on an inpatient basis over 1–3 days, similar to and often including the delivery of chemotherapy. Intralesional IL-2 is commonly used to treat in-transit melanoma metastases and has a high complete response rate. Local application In preclinical and early clinical studies, local application of IL-2 in the tumor has been shown to be clinical more effective in anticancer therapy than systemic IL-2 therapy, over a broad range of doses, without serious side effects. Tumour blood vessels are more vulnerable than normal blood vessels to the actions of IL-2. When injected inside a tumor, i.e. local application, a process mechanistically similar to the vascular leakage syndrome, occurs in tumor tissue only. Disruption of the blood flow inside of the tumor effectively destroys tumor tissue. In local application, the systemic dose of IL-2 is too low to cause side effects, since the total dose is about 100 to 1000 fold lower. Clinical studies showed painful injections at the site of radiation as the most important side effect, reported by patients. In the case of irradiation of nasopharyngeal carcinoma the five-year disease-free survival increased from 8% to 63% by local IL-2 therapy Toxicity Systemic IL-2 has a narrow therapeutic window, and the level of dosing usually determines the severity of the side effects. In the case of local IL-2 application, the therapeutic window spans several orders of magnitude. Some common side effects: flu-like symptoms (fever, headache, muscle and joint pain, fatigue) nausea/vomiting dry, itchy skin or rash weakness or shortness of breath diarrhea low blood pressure drowsiness or confusion loss of appetite More serious and dangerous side effects sometimes are seen, such as breathing problems, serious infections, seizures, allergic reactions, heart problems, kidney failure or a variety of other possible complications. The most common adverse effect of high-dose IL-2 therapy is vascular leak syndrome