Oral targeted therapy shows benefit in treating high-risk myelodysplastic syndrome

An oral targeted therapy gentle enough to be used by patients in their 70s or 80s is showing benefit in treating high-risk myelodysplastic syndrome (MDS), a pre-leukemic disorder that can progress to acute myelogenous leukemia (AML), according to a study presented at the annual meeting of the American Society of Hematology (ASH).

The drug R115777 (Zarnestra) (tipifarnib) produced responses that ranged from complete responses to improvement in blood counts in about one-third of 82 patients treated at seven different hospitals in the United States, Canada, and Europe, says the study's lead investigator, Razelle Kurzrock, M.D., a professor in the Department of Experimental Therapeutics at M. D. Anderson Cancer Center.

That level of response, as well as side effects that are well tolerated, can be a boon to the mostly elderly patients who develop the syndrome, Kurzrock says. "It is one more drug that can be tried to help improve blood counts and prevent leukemia development in these patients," she says.

At the time the study began, there was no approved therapy to treat MDS, but recently, the FDA approved use of azacytidine (Vidaza), which is a chemotherapy drug administered subcutaneously. Zarnestra helps about as many patients as Vidaza, "but for diseases like this, you need more than one drug because the syndrome is made up of numerous subtypes," Kurzrock says. "If one drug doesn't help, then the other might; or they could potentially be used together."

Zarnestra belongs to a group of drugs known as farnesyl transferase inhibitors, which block enzymes needed for the activation of cancer-promoting proteins. While the drug was initially believed to act primarily on the ras gene, which is mutated in about 25 percent of MDS patients, recent studies including this one demonstrate that patients whose ras gene is normal can benefit, Kurzrock says. "It has become apparent that Zarnestra regulates other important cancer genes, although we don't know which ones they are."