NEW ORLEANS--An antifolate that has been "shelved" for decades appears to be more potent than methotrexate(Drug information on methotrexate) in the treatment of childhood leukemias and could prove particularly helpful in patients who are not likely to respond to the traditional agent.
Dr. Barton Kamen, professor of pediatrics and pharmacology at the University of Texas Southwestern Medical Center, Dallas, compared methotrexate with a closely related but more toxic antifolate, aminopterin, in an in vitro study of radiolabeled drug uptake by lymphoblasts taken from acute lymphocytic leukemia (ALL) patients.
The study was initiated to foster understanding of drug resistance to meth-otrexate due to lack of accumulation in the cells, he said.
Dr. Kamen, a 1994 American Cancer Society (ACS) Clinical Research Professor, described his study at the ACS Science Writers Seminar.
He said that aminopterin was the first chemotherapeutic agent used for acute leukemia in childhood, the subject of a report by Dr. Sidney Farber in the New England Journal of Medicine in 1948. In the 1950s, it was replaced by methotrexate because of concerns over toxicity.
"Aminopterin was more toxic than methotrexate, and the toxicity was unpredictable; that was the problem. It was contaminated; it was not a pure drug," Dr. Kamen said. Today, aminopterin is available only through chemical supply houses.
Dr. Kamen's study has identified leukemic cells that accumulate folate in a "normal" manner, and cells that fail to accumulate methotrexate but do accumulate enough aminopterin to make treatment success likely with the older drug. "These data allow the suggestion that aminopterin, despite early reports of unpredictable toxicity, may be the better of the two antifolates," he said.