November 26, 2012
SAN FRANCISCO (The New York Times News Service) -- A global team of scientists led by Bay Area doctors is studying an unusual new technique -- involving, in part, injecting a genetically engineered smallpox vaccine directly into tumors -- that they hope will prolong the lives of patients with untreatable liver cancer.
If the therapy proves effective, it would be one of only two treatments available for people with liver cancer that has failed to be stopped by traditional chemotherapy and radiation, and for whom removal of the tumor isn't an option.
The treatment is still in a clinical trial and scientists note that other therapies that looked promising in the lab, and even in early human studies, eventually failed. But many doctors say the smallpox vaccine looks especially promising, partly because it's so effective at targeting and killing cancer cells and partly because decades of immunizations have shown the vaccine to be safe.
"Scientists basically took the smallpox vaccine and they tinkered with it and made it so it would only grow in cancer cells. It can't grow anywhere else in the body," said Dr. Ari Baron , the lead investigator of the clinical trial at California Pacific Medical Center. "That's the cool thing about it. It's been re-engineered to kill the cancer."
Liver cancer is not common in the United States, although rates of the disease have been climbing about 3.5 percent every year in the past decade, according to the Centers for Disease Control and Prevention. Nearly 29,000 cases of liver cancer are diagnosed in the United States each year and more than 20,000 people die.
But worldwide, it's the most common cause of cancer death, mostly because the primary cause of liver cancer is hepatitis B or C, both of which are widespread in parts of Asia and Africa. More than 700,000 people worldwide are diagnosed with liver cancer each year, and 600,000 people die, according to the American Cancer Society.
Liver cancer is notoriously difficult to treat, partly because it's so difficult to surgically remove the tumor, doctors say. Since liver cancer starts from cirrhosis, the organ is often heavily scarred and fragile by the time it's diagnosed, and it can be impossible to dig out cancer cells without injuring what little healthy tissue remains.
Also, since the liver plays a central role in metabolizing the toxic chemotherapy drugs used to treat other kinds of cancer, those same drugs often aren't as effective and have far worse side effects in liver cancer patients.
Further complicating matters is that, since it's so difficult to remove the tumors, scientists have a tough time harvesting useful samples of liver cancer cells for research. Just this month, the University of California at San Francisco announced that it is partnering with the Bili Project Foundation in San Francisco to open a liver cancer tissue bank to collect samples for scientists worldwide.
"Finding a new direction to approach this particularly challenging cancer type is critical," said Dr. Robin Kate Kelly , a gastrointestinal cancer specialist at UCSF who is helping put together the tissue bank. "Our conventional strategies haven't been nearly as successful with liver cancer.
"It's too early to know how this (smallpox virus) is doing. But it's certainly exciting to think of a different mechanism that might have some promise."
Liver cancer often is treated first with chemotherapy, which usually involves delivering the drugs straight into the tumor via the blood vessels that feed it. After a high dose of chemotherapy is injected, doctors close off the blood vessels, so that they're both poisoning and starving the tumor.
That treatment doesn't always work, or often stops working after several doses. If it fails, there's only one drug, sorafenib , approved specifically to fight liver cancer. Sorafenib blocks the tumor's ability to form new blood vessels to supply it with nutrients for growth.
But not everyone responds to the drug, and, in general, it only adds a few months to patients' lives. Plus, it can have unpleasant side effects like nausea and vomiting, severe stomach pain and blood in the urine or stools.
Patients are out of options when the sorafenib stops working or becomes too difficult for them to tolerate, they're out of options. Liver transplants can save them, but there aren't nearly enough organ donors to meet the needs of all cancer patients.
That's why doctors are hunting for something to offer in addition to sorafenib. The idea to use the smallpox vaccine -- which is made from the virus vaccinia -- to kill tumors came from the knowledge that viruses can sometimes cause cancer.
When viruses attack the body, they often alter the DNA of cells and cause those cells to replicate. It makes sense to use a virus to attack cancer because it's already attracted to cells that replicate quickly, said Dr. David Kirn , chief medical director of Jennerex , the San Francisco pharmaceutical company that is leading the clinical trials.
The vaccinia virus is a good candidate in the fight against liver cancer because it's already been tested in millions of people worldwide who have been immunized, and it's shown a special affinity for cancer cells, Kirn said.
The virus has been genetically altered to only target cancerous cells. Once they reach those cells, they'll attack them -- and only them -- while at the same time alerting the body's immune system and rallying white blood cells to the fight.
"The vaccinia virus already has a propensity for tumor cells, and then it's been DNA mutated to make it a tumor-killing machine," said Dr. John Rhee , a radiologist at California Pacific Medical Center who's involved in the smallpox vaccine study. "It will replicate and destroy cancer cells at the same time."
In the clinical trial -- which is being done at 47 sites worldwide, including California Pacific Medical Center and Stanford -- patients are randomly sorted into receiving the vaccine therapy or the current standard care, which is no treatment other than making the patient comfortable. An earlier study of just 30 patients, all of whom received the vaccine therapy but in varying doses, showed that more of the vaccine led to prolonged life.
But those results need to be repeated in a larger group of patients, which is what scientists are attempting now. They are hoping to enroll about 150 patients worldwide and complete it by the end of next year.
Patients who receive the vaccine in the current trial, which started earlier this year, begin with an intravenous injection, partly to prepare the body to mount an immune response. A week or two later, a radiologist injects more of the vaccine directly into the patients' blood, feeding the tumor. More of those injections follow at regular intervals for several months.
"If you think of breast cancer or colon cancer or other types of cancer, there's a deep bench of drug therapies. But liver cancer, there's only sorafenib," Baron said. "We want to be able to give something meaningful to patients. We want to make sure we have other treatments for them."
Copyright 2012 The New York Times News Service. All rights reserved.