Experimental medicine uses seek-and-destroy technique against tumor cells
WASHINGTON — A newfangled drug candidate featuring an antibody that totes a tumor-killing toxin can knock down ovarian cancer in some patients. In the first test of the experimental drug in people, scientists gave it to 44 patients with advanced ovarian cancer that was resistant to the effects of platinum-based chemotherapy, a standard treatment.
One patient showed what the researchers called a “complete response,” meaning any tumors became undetectable. Four other patients had a partial response, which means their tumors shrank by at least 30 percent, said Joyce Liu, a medical oncologist at Harvard Medical School. The results, presented April 6 at a meeting of the American Association for Cancer Research, represent a considerable improvement for a patient group with few treatment options.
“Most [ovarian] cancers will recur and become increasingly resistant to chemotherapy,” Liu said.
The experimental drug is called DMUC5754A. The sharp end of the stick in DMUC5754A is a toxin called monomethyl auristatin E, or MMAE, which must be wielded carefully. The toxin is “very, very powerful,” said Louis Weiner, director of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. MMAE disrupts microtubules inside cells, which are essential for all cells’ survival. That means the toxin must be tightly controlled when used inside the body. When attached to the antibody, Liu said, “MMAE is released inside the [tumor] cell and kills it.”
Liu’s early findings in patients suggest the antibody is capable of delivering the toxin where it is needed, Weiner said. Such conjugate therapies “are examples of where this field is going in the future,” he said.
The antibody portion of the compound binds to a large protein called MUC16 that shows up in 80 percent of ovarian cancers, Liu said. Only patients with high levels of MUC16 had a good response in this early trial, she said.
While that caveat may limit the number of patients who could benefit, it also means that tests showing high levels of MUC16 might reveal to doctors which cancer patients might best benefit from the experimental drug.
DMUC5754A appeared safe. Only two patients experienced side effects potent enough to require lowering their doses. Slightly more than half experienced fatigue, and about a third reported some nausea — both common side effects for anticancer drugs. Liu said DMUC5754A, which is being developed by the biotech company Genentech, will get further testing with larger groups of patients.
Ovarian cancer is the leading cause of death among gynecological malignancies in the United States, killing more than 14,000 patients each year.MUC16 also shows up in people who have pancreatic cancer, she said. Researchers are recruiting volunteers with pancreatic cancer to test the drug candidate.
J. Liu et al. Targeting MUC16 with the antibody-drug conjugate (ADC) DMUC5754A in patients with platinum-resistant ovarian cancer: A phase 1 study of safety and pharmacokinetics. Abstract LB-290. American Association for Cancer Research Annual Meeting, Washington, D.C., April 6-10, 2013.
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