About 30% to 40% of patients with recurrent head and neck cancer respond briefly to chemotherapy but the cancer frequently returns in an area where the patient has already been treated with radiation. Because more radiotherapy is not an option, doctors must find new ways to treat these patients. This new treatment, called ONYX-015, targets tumor cells and spares healthy tissue, unlike radiation therapy.

The study involved 40 patients with head and neck cancer that continued to grow or came back after chemotherapy, according to John Nemunaitis, MD, the study?s lead author and director of the gene cellular molecular program for U.S. Oncology in Dallas.

Patients were divided into two groups. The first group was given ONYX-015 injections directly into their tumor sites once a day for five consecutive days. The second group received injections twice a day for two consecutive weeks. In the first group, 14% of the patients had partial to complete regression, and 10% of the second group had complete regression, meaning their tumors were undetectable.

ONYX-015 is an altered adenovirus, one of the viruses that cause the common cold. A normal unaltered virus will infect a cell and take control of the cellular machinery, forcing it to make viral proteins. It is able to do this by inactivating a cell-defense protein called p53. The cell makes virus particles until it fills up and bursts, killing the cell and releasing more virus to infect the neighboring cells.

However, the ONYX-015 virus is missing the protein that inactivates p53, so it cannot take over normal cells. About 40% to 50% of head and neck tumor cells lack working (or functional) p53 protein, making them vulnerable to ONYX-015 infection.

Michael Thun, MD, vice president of epidemiological research and surveillance for the American Cancer Society, says the study is a step in the fight against cancer. "I would call it somewhat encouraging that both patient groups who were treated with this approach had improved courses compared to what might be expected," he says.

Although Thun points out that this trial involved a small number of patients, he says some relevant results were achieved. "Basically what they are doing is comparing two treatment schedules against each other and what they?re seeing is some possibly favorable preliminary results," says Thun.

A larger phase III study using the virus by itself is in the discussion stages, says Nemunaitis. And much bigger things may yet be in store for ONYX-015. "We know that if we have cancer cells in a laboratory, we can eradicate every single cancer cell with gene therapy," Nemunaitis says. "And if we have an animal with tumors on it, we can get enough genes into the tumor cells to cure the animal. When we take it to people, we have problems."

The problems, he says, stem from the fact that scientists are unable to get enough of the gene into the tumor cells. "We showed that we can detect this virus in the bloodstream several hours later and in some cases several days later," he says. "And that?s an important point because it means that the virus is circulating in the body over and over again, and it?s gaining access to cancer sites that are [far from] to the tumor site we injected."

Nemunaitis says this might allow the virus to act as a delivery system for cancer-killing or safety genes.

"The unique thing about this virus is not that it can replicate within the cancer cells, but that it can selectively replicate [in cells lacking the p53 protein]," he says. "If it could grow in the blood cells, it would kill them, too. But it doesn?t. And that?s just the point."