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CTLA-4 blockade with monoclonal antibodies in patients with metastatic cancer: surgical issues.

AbstractBACKGROUND:
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.
AuthorsGiao Q Phan, Jeffrey S Weber, Vernon K Sondak
JournalAnnals of surgical oncology (Ann Surg Oncol) Vol. 15 Issue 11 Pg. 3014-21 (Nov 2008) ISSN: 1534-4681 [Electronic] United States
PMID18716842 (Publication Type: Journal Article, Review)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Ipilimumab
  • tremelimumab
Topics
  • Antibodies, Monoclonal (adverse effects, therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD (immunology)
  • CTLA-4 Antigen
  • Clinical Trials as Topic
  • Enterocolitis (chemically induced, drug therapy)
  • Guidelines as Topic
  • Humans
  • Immunotherapy
  • Ipilimumab
  • Melanoma (drug therapy, pathology)
  • Neoplasm Metastasis

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