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Treating Hepatitis Infection and Liver Cancer Together

Tuma, Rabiya S. PhD

doi: 10.1097/01.COT.0000415894.16372.94


CHICAGO—Tremelimumab, an anti-CTLA4 antibody that takes the brakes off the immune system, may slow cancer progression and reduce hepatitis C viral load in patients with advanced liver cancer, researchers reported here at the American Association for Cancer Research Annual Meeting (Abstract 4387).

Chronic hepatitis C infection is the leading cause of liver cancer in Western countries, and once liver cancer gets to an advanced stage, the only approved therapy is sorafenib, which has limited impact on survival. Given those dual problems, Ignacio Melero, MD, PhD, a consultant in the department of oncology and a professor and senior investigator at Universidad de Navarra in Pamplona, Spain, and colleagues reasoned that it may be possible to improve patient outcomes by stimulating the immune system with tremelimumab.

To test the idea, the team enrolled 21 patients in a pilot study and treated 20 with 15 mg/kg intravenous tremelimumab every 90 days for a median of two cycles (range 1–4). Three patients discontinued treatment early, one due to clinical deterioration, one due to progression and early death, and one refused to continue due to diarrhea.

Of the remaining 17 patients evaluated for response, three had a partial response and 10 had stable disease lasting for at least six months. One patient remains on therapy. The median time to progression was longer than 4+ months.

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The treatment was not without side effects, however. The most common adverse effect was mild to moderate rash, which affected 40% of patients, and itching, which affected 45% of patients. Additionally, 30% of patients had elevated transaminases, with five of the seven cases reaching Grade 3 or higher. Low-grade fatigue, diarrhea, constipation, and anorexia affected 10% to 20% of the patients.

The treatment also appeared to alter the underlying hepatitis C infection over time. “We observed approximately one to two log drop in the hepatitis C viral load,” Melero said. “This clearly correlates with immune response against HCV in in-vitro testing. On an individual basis, some of the patients do much better and some even transiently completely clear the virus, which is interesting.”

He said that overall the investigators considered the drug to be well tolerated and potentially effective in this small study, even though patients had varying levels of liver dysfunction at baseline. “The data clearly tell us there is need for further clinical development in [hepatocellular cancer] for this strategy and, independently, this agent can be used to treat refractory hepatitis C infections.”

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No Further Plans for the Indication?

Although Pfizer supported the pilot study, neither that company nor MedImmune, which has licensed the antibody for oncology settings, appear to have specific plans to pursue the indication: “The Phase II trial results evaluating tremelimumab in patients with liver cancer reported at the AACR meeting...were based on a small patient size, which doesn't allow for any definitive conclusions,” a MedImmune spokesperson said via email. “But there seems to be a signal of activity with an acceptable safety profile which warrants further exploration. Currently MedImmune is evaluating tremelimumab in several different solid tumor indications.”

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.
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