Genetic Therapy - Proving Useful in
Treating Some Cancers
Cynthia Branch (left), Dr. Jack A. Roth and Dr. Gary L. Clayman check
experiments in the laboratory.
Dr. Jack A. Roth brought his dream for developing genetic therapy for human cancer when
he joined the M. D. Anderson faculty in 1986 as chairman of the Department of Thoracic and
Cardiovascular Surgery.
Today, he directs the most ambitious program for gene therapy and molecular therapeutics
in the world. At the close of the fiscal year, 38 investigators from diverse basic science
and clinical disciplines were involved in the translational research program.
"M. D. Anderson provides an unparalleled opportunity to conduct comprehensive
clinical research. The faculty are fortunate to have superb institutional support and
shared resources, which help us compete well for government grants and private
funds," observes Dr. Roth, who holds the Bud Johnson Clinical Chair and also is a
professor of tumor biology.
Dr. Roth's group described the first successful correction of a defective p53 tumor
suppressor gene in advanced lung cancer in the September 1996 issue of Nature Medicine.
This landmark report outlined how a retroviral vector, which doesn't cause human disease,
was manipulated in the laboratory and used to inject normal p53 genes into the lungs of
patients with non-small-cell lung cancer that had not responded to conventional therapies.
In an early (Phase I) clinical trial using an adenoviral vector to restore normal p53
function, 21 advanced lung cancer patients received the gene therapy. As anticipated, the
study confirmed previous observations in experimental animals, which showed the technique
was safe and did not cause any serious side effects. Each of the 21 patients received
escalating doses of the p53 treatment once a month. Nine of them also were given
intravenous doses of the drug cisplatin three days before being injected with the p53
gene.
While efficacy was not the primary goal of that first study, Dr. Roth and his colleagues
were encouraged to find that treated tumors in five patients who received escalating doses
of the p53 gene stopped growing and a sixth one had a partial response that lasted more
than six months. In addition, the combined p53 gene and cisplatin treatments halted tumors
from spreading for up to six months in eight patients.
The p53 gene injections also were studied in a Phase I clinical trial involving 33
patients with end-stage head and neck cancers. Dr. Gary L. Clayman, associate professor of
head and neck surgery, directed this study, which was divided into two treatment groups.
He says one group of 18 patients received only the p53 gene injections, but a second
group of 15 patients had surgery in addition to the gene therapy. Of the 15 patients
undergoing surgery, five remained disease-free for more than six months.
"The latter group includes one patient who has been in remission just over two
years and another man who has been free of disease for 21 months," Dr. Clayman says.
Elwood A. Mueller is the longest-surviving head and
neck cancer patient on the p53 gene therapy study.
The longest-surviving head and neck cancer patient on the p53 gene therapy study is
Elwood A. Mueller, who owns a ranch in Carmine in central Texas. To Dr. Clayman's delight,
Mueller recently passed the two-year mark after taking the gene therapy regimen - and he
also celebrated the 50th anniversary of being married to his wife, Bernice.
During the past year, Dr. Roth says more than 100 cancer patients were treated with the
adenoviral p53 gene therapy method. Phase II trials began combining p53 gene replacement
and radiation therapy for lung cancer patients. His technique is being applied to patients
with prostate, bladder, liver and breast cancers.
Tests of other gene therapy approaches are under way for M. D. Anderson patients with
breast and ovarian cancers and primary brain tumors.