An ongoing phase I clinical trial shows
that a new anticancer agent, CCI-779, is well-tolerated and may have
antitumor activity. CCI-779 is a derivative of rapamycin, an
immunosuppressive agent. Results of the study were presented at the
International Conference on Molecular Cancer Therapeutics sponsored
by the American Association of Cancer Research (AACR), National
Cancer Institute (NCI), and European Organization for Research and
Treatment of Cancer (EORTC). Jerome Alexander, a
physician-in-training and researcher working with senior
investigator, Eric Raymond, MD, made the presentation.
By interfering with key proteins that regulate cell growth,
CCI-779 may stop the progression of tumors. This is a unique
mechanism of action for an anticancer agent, said Dr. Raymond,
associate professor of oncology at the Institut Gustave Roussy in
Villejuif, France. If these preliminary results are confirmed
in future observations, this may represent a new and safer treatment
for cancer patients.
For this ongoing phase I study, 12 patients received CCI-779. Three
patients with renal cell cancer experienced tumor regression after
other treatments had failed. At the doses used so far, the main
adverse effects of CCI-779 have been mild skin reactions and
inflammation of the mucous membranes, which occurred at all dose
levels studied but did not increase in intensity with higher doses or
longer duration of treatment.
The new agent appears to block the effect of mTOR, an enzyme that has
an important role in regulating the synthesis of proteins that
control cell division. Therefore, CCI-779 may stop the production of
proteins essential for cancer cell proliferation and possibly
survival of cancer cells. According to the researchers, ongoing
studies are evaluating other dose levels and a longer treatment
duration to confirm the safety and efficacy of CCI-779 before
advancing to phase II studies to confirm efficacy in several types of cancer.
Axel Hanauske, MD, PhD, from the Oncology Institute in Munich,
Germany, and the sponsor, Wyeth-Ayerst Research in Radnor,
Pennsylvania/Genetics Institute in Munich, Germany, are collaborating
on the study.