CTLA-4 Blockade with Monoclonal Antibodies in Patients with Metastatic Cancer: Surgical Issues |
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Authors: | Giao Q Phan Jeffrey S Weber " target="_blank">Vernon K Sondak |
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Institution: | (1) Division of Cutaneous Oncology, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA;(2) The Donald A. Adam Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA;(3) Department of Oncologic Sciences, University of South Florida College of Medicine, Tampa, FL, USA;(4) Department of Surgery, University of South Florida College of Medicine, Tampa, FL, USA |
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Abstract: | Background CTLA-4 (cytotoxic T lymphocyte–associated antigen 4) is a modulatory receptor on T cells involved in downregulating T cell
activation. In animal models, CTLA-4 blockade abrogates tolerance to “self” antigens, resulting in the augmentation of antitumor
immunity and induction of autoimmunity. CTLA-4 blockade by means of monoclonal antibodies (ipilimumab and tremelimumab) has
been evaluated in multiple clinical trials in patients with metastatic cancer, mainly those with melanoma and renal cell cancer.
Methods We examine available literature and ongoing clinical trials with ipilimumab and tremelimumab and review our own experience
with patients treated with CTLA-4 blockade, with an emphasis on issues of direct relevance to surgical oncologists.
Results CTLA-4 blockade can cause durable tumor regression in patients with metastatic melanoma and other solid tumors. Grade III/IV
autoimmune toxicity has been frequently encountered in clinical trials and includes enterocolitis, dermatitis, hypophysitis,
uveitis, and hepatitis. Enterocolitis is the most common immune-related adverse event and may cause severe diarrhea requiring
intravenous hydration, high-dose corticosteroids, and blockade of tumor necrosis factor alpha with infliximab. Most patients
respond to medical treatment, but up to 12% with grade III/IV enterocolitis develop perforation or bleeding that requires
colectomy.
Conclusions As more patients are enrolled onto clinical trials involving ipilimumab and tremelimumab, an increasing number of surgeons
may be involved in the care of these patients who develop treatment-related complications. In this report, we review the rationale
for CTLA-4 blockade and review selected clinical studies published so far with ipilimumab and tremelimumab. We offer guidelines
on the management of patients who develop enterocolitis. |
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