Aug. 21, 1998 Researchers at the UCSF Cancer Center are recruiting patients with advanced lung cancer for a clinical trial of a novel drug that they hope will inhibit the growth and spread of cancer.
The drug, developed by Agouron Pharmaceuticals, Inc., is one of the first agents in a new class of therapies that have been shown to inhibit the actions of a natural body chemical, called Matrix Metalloproteases (MMPs), that breaks down the material between cells to make room for new cellular growth.
There is good reason for enthusiasm about this drug because the preliminary data looks favorable and suggests that MMPs inhibitors (MMPIs) are effective in slowing tumor growth, said David Jablons, MD, UCSF assistant professor of surgery and principal investigator of the study.
The inhibitors are also well tolerated because they are taken in pill form and have minimal side effects. In a normal, healthy body, MMPs play an important role in such processes as fetal development, ovulation, wound healing, and cell growth and regeneration.
However, when too many MMPs are produced or are present at the wrong time, they can break down the material, known as extracellular matrix, that holds cells together inside tissues.
This activity occurs in diseases in which healthy tissue is broken down or unhealthy tissue grows, as in cancer and rheumatoid arthritis, Jablons said.
Cancer tumors grow and spread, interfering with the functions of healthy tissue. Some MMPs have been shown to play a significant role in tumor development by contributing to three processes that lead to the progression of cancer: invasion, metastasis, and angiogenesis.
Cancer researchers believe that a MMPI, called AG3340, will block these processes while limiting the damage that may result from a broad suppression of MMPs.
Invasion is the expansion of tumors into neighboring healthy tissue. MMPs act to break down the matrix structure of the healthy tissue, paving the way for the invading malignant tumor.
Metastasis is the spread of tumor cells to distant locations in the body. MMPs loosen the tissue structures, permitting cancer cells to break off and spread to other locations where they can grow. In addition, the breakdown of tissues themselves trigger the release of more MMPs, which promotes further tumor growth and expansion.
Angiogenesis is the development of new blood vessels. As a malignant tumor grows, it requires the development of blood vessels to supply its nutrients and oxygen. MMPs help these new vessels to grow by breaking down the matrix to pave the way for advancing blood vessels.
During the clinical trial of the MMPI, participating patients will be randomized to receive either a pill form of the drug or placebo in combination with chemotherapy infusions. This is a multicenter, phase III study, the stage of a trial designed to determine the drug1s effectiveness.
To quality for the trial at UCSF/Mount Zion, part of UCSF Stanford Health Care, patients must have advanced non-small cell lung cancer, a recurrence of the disease following surgery or radiation therapy, and have had no previous chemotherapy treatments.
Patients may experience side effects related to the MMPI including fatigue, joint stiffness, joint swelling, and, in a few patients, some limits on the mobility of certain joints, most often the shoulders and hands.
Those who are interested in participating in the trial should contact the UCSF Cancer Center trial coordinator Greg David at (415) 885-7283.
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