Mortality rates for most cancers are declining, but liver cancer deaths are rising due to the number of people with hepatitis B and C. These viral infections increase the risk for developing liver cancer, known as hepatocellular carcinoma (HCC).
Liver cancer, which can be difficult to treat, is the fifth-leading cause of cancer deaths worldwide.
Combining old procedure with new drug
However, researchers at UC Irvine Chao Family Comprehensive Cancer Center are testing an innovative treatment that combines a standard procedure with a new drug. UCI is the lead research site for a nationwide phase 2 clinical trial called TATE, which studies the effects of the experimental anti-cancer drug tirapazamine (TPZ) when combined with a procedure called embolization that cuts off blood to the tumor.
TPZ was initially studied in cancers such as non-small cell lung cancer in the 1990s without significant success, says Dr. Nadine Abi-Jaoudeh, a UCI Health interventional radiologist and the trial’s lead investigator.
Drug activated in low oxygen
The drug’s unique nature — it is activated in low-oxygen environments, creating cancer-killing free radicals — made it an intriguing subject for liver cancer. That’s because liver cancer cells depend on the body’s network of blood vessels to grow, with the tumors usually developing around the artery that feeds oxygen-rich blood to the liver.
Liver cancer patients typically are treated with a procedure called transarterial chemoembolization, or TACE. It works by delivering chemotherapy at the same time it cuts off the tumor’s blood supply. At least 30 percent of the tumor cells die in half the people who undergo TACE.
However, complete tumor death occurs in only 26 percent of TACE patients. Overall, TACE extends survival an average of two years.
Killing more tumor cells
But Abi-Jaoudeh recognized the potential for a synergistic effect by adding the low-oxygen activated TPZ to the standard procedure. The anti-cancer drug may kill more tumor cells than with TACE alone because it can take advantage of the oxygen-starved environment created when the blood supply is cut off by embolism.
“TACE is currently one of the best treatment options for intermediate hepatocellular carcinoma, but it presents a major challenge,” says Abi-Jaoudeh.
“Embolization kills some of the tumor cells, extending life for a short amount of time. But that process ends up naturally selecting tumor cells that can survive without oxygen, so when the cancer reoccurs it is less responsive to TACE.”
FDA considering accelerated approval
In an earlier phase 1 trial of TATE, Abi-Jaoudeh combined tirapazamine and embolization, showing that the combination produced a higher response rate than TACE — embolization and chemotherapy —alone. Moreover, the treatment was well tolerated by patients.
Based on the earlier data, the U.S. Food and Drug Administration recently agreed to consider the results of the current phase 2 trial for accelerated approval, which would make a phase 3 trial unnecessary.
“So far, our results have shown it to be safe, with a very positive index in terms of response. We’ve seen complete response in 65 percent of patients and an overall response of 90 percent,” she says. “In phase 2, we hope to further confirm the responses to this approach that we saw in phase 1.”