Warren Chow, M.D., associate professor of medical oncology, is conducting a clinical trial that takes a unique and original approach to treating cases of liposarcoma, a cancer that develops in the fat cells. City of Hopes treats close to 15 cases each year, and more than 1,500 people in the U.S. are diagnosed with liposarcoma annually.
Most cases of liposarcoma occur in the abdomen or thighs, and treatment commonly includes surgery, chemotherapy and radiation. Depending on the location of the tumor, though, surgery is not always possible. Chemotherapy has been shown to be effective for only about 40 percent of liposarcoma cases, and many patients suffer recurrence despite therapy. Chow saw the benefits and limitations of current treatment options, then looked at treating liposarcoma from a different perspective.
“Patients with HIV infection taking HIV protease inhibitors may develop a condition known as lipodystrophy, in which the body’s fat is redistributed and can be lost, as a side effect,” said Chow. “I thought that effect might be useful against liposarcoma, which is an abnormal growth of fat cells.”
Chow was the first to propose the use of HIV protease inhibitors on liposarcoma, and is the first to conduct a clinical trial. The National Cancer Institute is simultaneously conducting research into the use of HIV protease inhibitors to treat a variety of cancerous tumors, including lung and breast.
Laboratory tests showed the HIV protease inhibitor nelfinavir, made by Pfizer Inc. under the trade name Viracept, had the most potent effect on tumor tissues. In order to advance his research and test whether nelfinavir would be an effective treatment for liposarcoma, Chow submitted a proposal to the U. S. Food and Drug Administration (FDA), and was awarded a grant from the FDA’s Orphan Products Development Grants Program for a three-year study.
City of Hope’s Office of Technology Licensing approached Pfizer about the clinical trial using nelfinavir to see if Pfizer was interested in donating drug for the study.
“Our Office has regular contact with pharmaceutical and biotech companies since many of City of Hope’s scientists and physicians are conducting research using experimental cancer drugs,” said Brian Clark, Ph.D., director of the Office of Technology Licensing, who lead the negotiations with the drug company. “Pfizer recognized the merits of the study and generously donated nelfinavir for the trial.“
Chow is currently enrolling liposarcoma patients in a phase I/II clinical trial of nelfinavir for liposarcoma. The phase I trial will examine dosage and safety levels, and after those results are analyzed, Chow expects to move on to the phase II efficacy trial. “We’re looking at any hint, any positive signal, that nelfinavir might have a benefit for patients with recurrent liposarcoma,” he said.
Chow also is conducting correlative research on surrogate markers in normal fat tissue. Patients enrolled in the clinical trial will undergo a biopsy of normal fat tissue. The investigators will examine this to see how nelfinavir affects normal fat cells on the molecular level. Because serial biopsy of tumor tissues can be difficult as they are often deep within the body, these molecular marker studies will serve as a surrogate for what Chow believes is happening in the tumor. If a tumor is readily accessible, however, the researchers will try to re-biopsy while the patient is taking nelfinavir. These studies “may help us determine who is most likely to benefit from treatment with nelfinavir,” said Chow.
