Gastrointestinal Perforations Associated With Interleukin-2 Administration

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Abstract
High-dose interleukin-2 (IL-2) results in objective clinical regression in up to 17% of patients with metastatic melanoma and renal cell carcinoma, with about half of these patients experiencing a complete regression of all lesions. Gastrointestinal (GI) perforation is a rare but potentially serious complication of IL-2 administration. A retrospective review of all patients treated with IL-2 in the Surgery Branch of the National Cancer Institute (NCI) between Nov. 1, 1984, and May 1, 2002, was performed. In addition, a review of the published English literature on GI perforation in conjunction with IL-2 therapy was performed. Among the 1,797 patients treated at the NCI, there were eight (0.44%) cases of GI perforation. Seven of the eight patients were treated with high-dose (720,000 IU/kg every 8 hours) intravenous IL-2 (7/1,680, 0.42%) and one was treated with subcutaneous IL-2 (1/117, 0.85%). These patients developed various signs and symptoms of GI perforation. Six patients developed abdominal pain, yet only two of the eight patients had a fever. All six patients who underwent radiographic evaluation prior to diagnosis had free intraperitoneal air seen on the study. The location of the perforation included the stomach, small bowel, appendix, and colon. All underwent surgical treatment successfully, and four patients received further IL-2 therapy after recovering from the perforation. With the patients presented in this article, there have now been 20 cases reported in the English literature. Two of the patients at the NCI had a ruptured appendix, which has not been previously reported in the literature. The key to early diagnosis of GI perforation during IL-2 therapy is radiographic evaluation. Patients with GI perforation can be safely retreated with IL-2 if they are given adequate time to recover from their surgical intervention and if careful assessment is performed to rule out residual infection.

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