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Aminopterin, First Studied in 1948, Appears Poised for Comeback in ALL

Aminopterin, First Studied in 1948, Appears Poised for Comeback in ALL

NEW ORLEANS--An antifolate that has been "shelved" for
decades appears to be more potent than 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.

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