IL-1 Antagonists May Offer a Potential Cancer Treatment

IL-1 antagonists are traditionally used to treat patients with rheumatoid diseases.

Anakinra is an interleukin antagonist used to treat patients with rheumatoid arthritis, but has more recently been studied as a part of a combination therapy for certain cancers.

The drug’s role in cancer treatment is increasing, as the IL-1 receptor antagonist is currently being investigated in acute myelogenous leukemia, colorectal cancer, prostate cancer, and multiple myeloma, according to a session presented at the American College of Rheumatology and Association of Rheumatology Health Professionals annual meeting.

Anakinra was approved by the FDA for the treatment of rheumatoid arthritis in 2002, and has since received approval for multiple other diseases. The drug inhibits the IL-1 receptor, which blocks IL-1 beta and IL-1 alpha.

Other conditions have been seen to benefit from anakinra, including osteoarthritis, gout, and macrophage activation syndrome. In patients with cancer, IL-1 promotes angiogenesis and invasiveness, and may even play a role in immune response suppression, according to the session’s speaker Charles Dinarello, MD, professor of medicine and immunology at the University of Colorado School of Medicine, and professor of experimental medicine at Radboud University in the Netherlands.

Dr Dinarello has trained more than 50 researchers, and was named the fourth most-cited scientist from 1983 to 2002, reinforcing his vast knowledge.

IL-1 beta has been shown in hematopoietic cancers, such as acute myelogenous leukemia, multiple myeloma, Hodgkin’s disease, and B-cell leukemias, while IL-1 alpha has been shown in mesenchymal epithelial cancers, such as breast, prostate, lung, colon, and pancreatic cancers, as well as melanoma.

“All healthy mesenchymal and epithelial cells contain the IL-1 alpha precursor, and normal platelets contain IL-1 alpha,” Dr Dinarello said. “The IL-1 precursor is active and upon cell death, IL-1 alpha is released and it triggers immediate inflammation.”

Other IL-1 receptor antagonists have been used in clinical trials to treat other diseases, including canalinumab and rilonacept, which inhibit IL-1 beta, and xilonix, which inhibits IL-1 alpha. In a phase 3 study, investigators evaluated the use of xilonix plus chemotherapy in patients with late-stage metastatic colorectal cancer, and found that it increased overall survival.

Patients who responded to 4 biweekly infusions of xilonix had an overall survival of 11.5 months, compared with 4.2 months in patients who did not respond to the treatment, Dr Dinarello reported.

Thus far, anakinra has been used to treat patients with pancreatic and breast cancers, gout, macrophage activation syndrome, pre-multiple myeloma, idiopathic pericarditis, Kawasaki disease, post-myocardial heart failure, and decompensated heart failure, according to the session.

Canakinumab has been successful in treating gout and cardiovascular events, and rilonacept has been used to treat kidney failure. Xilonix has been used to treat late-stage cancer, psoriasis, and type 2 diabetes.

These IL-1 antagonists offer much benefit to patients with rheumatoid diseases, and could also present another treatment option for patients with advanced cancers.