NEW YORK (Reuters Health) - Intratumoral injection of human wild-type p53 (Advexin; Introgen Therapeutics) combined with induction chemotherapy (docetaxel and doxorubicin) has impressive therapeutic activity in locally advanced breast cancer, a new study shows.
Dr. Massimo Cristofanilli from The M. D. Anderson Cancer Center in Houston reported his team’s findings Wednesday during the 27th annual San Antonio Breast Cancer Symposium.
About half of all women with locally advanced breast cancer have mutations in the tumor suppressor gene p53, he explained in a telephone interview with Reuters Health. Advexin therapy uses an adenovirus vector to shuttle high concentrations of normal p53 to tumors.
In the current study, 12 women with locally advanced breast cancer (stage IIIB) received up to 6 cycles of intratumoral Advexin injections plus docetaxel and doxorubicin before surgery. This treatment led to a greater than 50% reduction in tumor size, from a mean size of 8 cm to 1.78 cm, in all of the women.
“Every patient that received Advexin plus chemotherapy responded to the treatment; and this is an uncommon finding with locally advanced disease,” Dr. Cristofanilli said.
Examination of excised tumors showed significant infiltration of T-lymphocytes, suggesting that Advexin produced an extensive immunological local response in the breast, Dr. Cristofanilli reported. “This is obviously a finding that is quite new for a local treatment for the breast, and we think this constitutes actually the benefit of the treatment itself,” he said.
The investigators also observed an increase in p53 mRNA with Advexin therapy, indicating that “this therapy is producing biologically what we expect it to,” Dr. Cristofanilli noted.
The next step will be to determine “how superior Advexin plus chemotherapy is to chemotherapy alone,” Dr. Cristofanilli said. “Based on the fact that we have only one death so far, and we are approaching 28 months of follow up, I would say that this appears to be very promising.”
“If a 75% to 85% survival at 5 years is achieved, obviously this is much superior to what we can see with chemotherapy alone and it indicates that additional mechanisms play a role in this response, including probably an immunological phenomenon. That’s why we need to actually compare this approach with chemotherapy alone,” he explained.
MeSH Headings:Biological Therapy: Congresses: Health Care Economics and Organizations: Genetic Engineering: Genetic Techniques: Investigative Techniques: Organizations: Therapeutics: Gene Therapy: Genes, p53: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Health CareCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
