Drugs Log

The cancer drug cyclophosphamide activates a viral infection that helps anti-viral medications eliminate a virus-linked cancer, says a new study.

The drug is used to treat Burkitt lymphoma, an aggressive, fast-growing type of non-Hodgkin lymphoma that often occurs in children. In Africa, the cancer is caused by the Epstein-Barr virus (EBV), which typically remains dormant inside tumor cells.

This study of 21 patients, ages 5 to 15, who were being treated with cyclophosphamide, found that the drug triggers an active EBV infection. Increased replication of the virus in cancer cells makes the cells more susceptible to antiviral drugs, which kill cells containing the replicating virus.

The study was published in the April issue of the journal Clinical Cancer Research.

“What we have learned from this work is a potential means of capitalizing on presence of viral genomes within tumor cells to alter those tumor cells in a way that makes them more susceptible to treatment. Our findings have implications for other EBV-related malignancies that, overall, are among the most common cancers worldwide,” Dr. Margaret Gulley, a professor of pathology and laboratory medicine at the University of North Carolina at Chapel Hill School of Medicine, said in a news release.

EBV infects more than 90 percent of people worldwide and is associated with a number of diseases including lymphomas, gastric cancer, and nose and throat cancer.

The next step in this research is a clinical trial to test the use of a cancer drug and an antiviral drug simultaneously, Gulley said.

Researchers have reached a deeper understanding of how tumours actively suppress immune responses in their immediate environment, which can dampen responses to cancer vaccines. To overcome this, some therapies currently in development combine the vaccine with chemotherapies that are designed to counteract this immune suppression. For example, a Seattle-based biotechnology company called Oncothyreon has developed a cancer vaccine called Stimuvax that is administered in combination with the drug cyclophosphamide. The compound inhibits immune cells called T-regulatory cells, which block immune responses to the body’s own molecules.

Compounds that modulate the immune response could have unwanted side effects, however. A patient in a clinical trial of Stimuvax involving high doses of cyclophosphamide developed an acute inflammation of the brain, which caused the FDA to put all Stimuvax trials on hold.

A clean safety profile is crucial if cancer-vaccine developers are to improve a vaccine’s performance in clinical trials. To date, most of these trials have enrolled patients who are in the advanced stages of cancer, which may have limited the trials’ effectiveness because such individuals may not be able to mount an effective immune response. Now that such vaccines have been established as safe in phase II trials, clinicians are more willing to test them in healthier patients. An ongoing large trial of a lung cancer vaccine by London-based pharmaceutical firm GlaxoSmithKline, for example, is enrolling patients at an earlier stage of the disease.

For some in the field, the struggle to create effective cancer vaccines conjures up memories of the long battle to develop antibody-based therapies, which are now a mainstay of the biotechnology industry. There, too, a series of clinical-trial failures initially soured the field’s reputation, recalls Thomas Davis, chief medical officer at Celldex. In the early 1990s, when Davis worked to develop rituximab — a monoclonal antibody used to treat autoimmune disorders and some cancers — he recalls that researchers in the field learned to be resilient. “We realized you just have to test a lot of drugs to find one that works,” he says, “and it’s the same for a cancer vaccine.”