To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: First Gene Therapy Study Show Tumor Regression In Head and Neck Cancer URL: http://www.pslgroup.com/dg/2889E.htm Doctor's Guide May 20, 1997
DENVER, May 19, 1997 -- Researchers from The University of Texas M.D. Anderson Cancer Center reported that the first gene therapy study using the tumor suppressor p53 gene was safe and showed evidence of clinical activity in patients with head and neck cancer, according to Phase I data presented here today at the 33rd American Society of Clinical Oncology (ASCO) Annual Meeting. "This trial was designed to study the safety of increasing doses of in vivo (inside the body) gene therapy in recurrent head and neck cancer. The treatment appears to be safe and did not cause any serious side effects," said Dr. Jack Roth, Chairman of the Department of Thoracic and Cardiovascular Surgery at M.D. Anderson Cancer Center. "The p53 treatment also resulted in tumor regression in several patients who could not undergo surgery for their recurrent tumors. Most patients who had surgery and p53 treatment have remained free of their tumor for a prolonged period of time. These results are preliminary, but encouraging. Based on these results, Introgen and RPR Gencell plan to initiate a Phase II clinical trial in the United States in the second half of 1997. Cancers of the head and neck account for over 120,000 new cases each year. These cancers primarily include squamous-cell carcinoma of the oral cavity, pharynx and larynx. The disease is disfiguring and has debilitating effects on speech, swallowing and cosmetic appearance. The overall rate of survival of these patients has remained unchanged over the three decades since the advent of contemporary surgery and radiotherapy. While surgery and radiation therapy can cure early stages of this disease, a majority of all patients relapse, and development of a recurrent tumor is almost always fatal within one year. Clinical Trial Results In this Phase I trial, conducted at M.D. Anderson Cancer Center, Houston, Texas, by principal investigator, Dr. Gary L. Clayman, 30 patients with advanced recurrent squamous carcinoma of the head and neck were enrolled. All were end-stage patients who had failed conventional treatments. The study was a dose escalation trial; each of the 30 patients was injected with p53 gene via an adenovirus delivery system (vector) directly into the tumor. There were two treatment groups. The resectable (operable) group received Adenoviral-p53 (Ad-p53) every other day for two weeks (6 injections), had intra-operative injection at the time of the resection (72 hours post injection 6) and received an additional injection 72 hours post surgical resection. The non-resectable (non-operable) group received Ad-p53 every other day for two weeks (6 injections), were observed for two weeks and then repeated the treatment cycle. This group continued treatment until progression. No adverse side effects attributable to the p53 gene were observed in any of the 30 patients. Of the 17 non-resectable patients, five were stable and two exhibited partial regression, defined as at least a 50% reduction in injected tumor at the end of the trial. Of the 13 resectable patients only 3 patients have died of cancer, five or 38% remain free of disease for more than 6 months post-therapy, defined by a total disappearance of all measurable signs of cancer. At the time of surgery, one patient demonstrated a complete pathological response to Ad-p53. "This trial demonstrates safety as well as clinical activity for the Ad-p53 gene therapy treatment and validates the work that we have been conducting here at M.D. Anderson," said Dr. Roth. Role of p53 Over 50 percent of all cancers have a mutation in the p53 gene. p53 is a tumor suppressor gene that encodes a protein which responds to damage involving a cell's DNA. The protein activates one of two pathways in the damaged cell: a) a growth-arrest pathway, in which cell division is halted until the DNA damage has been repaired or b) a cell-suicide or apoptotic pathway, in which heavily damaged cells undergo programmed cell death. Each of these pathways prevents mutations from being passed on to daughter cells and are important brakes in the development of certain cancers. These protective pathways become non-functional when a cell's own p53 genes are lost or mutated. Data produced in this clinical study suggest that Ad-p53 therapy may benefit cancer patients bearing tumors without p53 mutations. Introgen Therapeutics and RPR Gencell Introgen Therapeutics, Inc., an Austin-based company engaged in the development of cancer therapeutics, sponsors Drs. Roth and Clayman along with 25 other clinicians and researchers at M.D. Anderson Cancer Center. Introgen and RPR Gencell, the gene therapy division of Rhone-Poulenc Rorer, are collaborating to develop and commercialize gene therapy products based on the p53 pathway and k-ras oncogene inhibition. Introgen Therapeutics, Inc., a leader in the development of gene-based cancer therapeutics, is a privately held company formed to commercialize anti-cancer technology developed at the University of Texas M.D. Anderson Cancer Center in Houston, Texas. Introgen's primary focus is the development of in vivo gene therapy products for a variety of cancers and development of vectors used to deliver genetic material constructs. Introgen is currently conducting Phase I/II clinical study protocols in the United States. RPR Gencell and Introgen are planning to conduct additional Phase I/II clinical trials in various indications in the United States, Europe and Japan during 1997. Introgen and RPR Gencell plan to commence a Phase II trial in head and neck cancer in North America during 1997. RPR Gencell is the division of Rhone-Poulenc Rorer dedicated to the discovery, development, manufacture and commercialization of gene therapy products. By linking leading biotechnology companies and research organizations worldwide with its own internal capabilities, RPR Gencell hopes to accelerate the development of effective therapies for cancer, cardiovascular disease, central nervous system disorders and asthma. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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