PHILADELPHIA--The use of all-trans-retinoic acid (RA, Vesanoid)
in-duces a very high incidence of complete remission in patients
with acute promye-locytic leukemia (APL) who have not received
previous retinoid therapy.
Raymond P. Warrell, Jr., MD, of Memorial Sloan-Kettering Cancer
Center, said that in the approximately 120 patients he has treated
with RA over the past 6 years, overall survival of newly diagnosed
patients has almost tripled, compared with chemotherapy alone.
Dr. Warrell discussed his findings at Fox Chase Cancer Center's
12th Annual Toward 2000 Symposium.
Conventional chemotherapy has produced overall survival rates
of only 25% to 30%, Dr. Warrell said. With therapy based on RA,
he has achieved a complete remission rate of about 85%. He says
the only patients who do not go into complete remission are those
who die early or who were misdiagnosed.
Retinoic acid is used for induction therapy, followed by conventional
consolidation therapy with a full course of an anthracycline-containing
regimen with or without cytarabine, then by two more abbreviated
courses of the same drugs after the patient has recovered from
Dr. Warrell believes RA should be used as first-line therapy,
and no patient should be treated with chemotherapy alone.
"It's curious that in the United States the drug is approved
only for treatment of relapsed patients, in which there really
is no survival advantage whatsoever," he said, "whereas
every study in which the drug has been employed up front has shown
a major advantage with respect to chemotherapy alone, and that's
why it is now generally accepted as the standard of care."
The drug's mechanism of action appears to be differentiation.
Based on cellular morphology and surface markers, Dr. Warrell
finds that, "it induces differentiation and maturation of
leukemic cells such that these cells grow up, grow old, and then