Gene therapy increases survival for end-stage head and neck cancer

A gene therapy invented at The University of Texas M. D. Anderson Cancer Center is the first to succeed in a U.S. phase III clinical trial for cancer, as announced today at the American Society of Gene Therapy annual meeting in Boston.

Introgen Therapeutics, Inc., reported results of its phase III trial of Advexin(r), a modified adenovirus that expresses the tumor-suppressing gene p53, for end-stage head and neck cancer.

"Cells become cancerous because p53 no longer functions. Restoring p53 works unlike any current cancer treatment because it treats the cancer genome," said Jack Roth, M.D., professor in M. D. Anderson's Department of Thoracic & Cardiovascular Surgery, who invented the drug and co-founded Introgen. He remains a shareholder and paid consultant to Introgen, and the University of Texas System is also a shareholder in Introgen.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

The trial showed that p53 expression in the patient's tumor before treatment is a reliable biomarker for how to treat head and neck cancer. Patients with a favorable p53 profile who received Advexin(r) had a median survival of 7.2 months, compared with 2.7 months for those whose tumor expressed high levels of mutant p53 before treatment. Patients with this unfavorable profile were better off taking the chemotherapy drug methotrexate, resulting in median survival of 5.9 months.

"The important finding is that patients who benefit from treatment can be identified with the p53 biomarker. The biomarker will enable physicians to personalize treatment," said Roth, who also directs M. D. Anderson's W.M. Keck Center for Innovative Cancer Therapies.

Detailed results of the 123-patient clinical trial, led by John Nemunaitis, M.D., executive director of the Mary Crowley Medical Research Center at Baylor-Charles A. Sammons Cancer Center in Dallas, are available at www.introgen.com.

Better Quality of Life

Patients treated with Advexin experienced far fewer harmful side effects such as pneumonia than those who received methotrexate. The incidence of inflammation of the mouth lining and a decrease in white blood cells, for example, both dropped to zero for those receiving Advexin.

"That certainly results in a better quality of life," Roth noted, which makes sense because p53 does not cause problems in normal cells.

Roth's lab has been developing gene therapy for cancer since 1990. "We wanted to go beyond conventional treatment, because most of those treatments were not very effective," Roth said. "Surgery and radiation are limited to the local tumor and once given, it's very hard to repeat those therapies. Chemotherapy inhibits DNA replication, but it also interferes with normal cells."