ROCKVILLE, Md--The FDA Oncologic Drugs Advisory Committee has
recommended approval of two agents: Hoffmann-La Roche's Vesanoid
(tretinoin, all-trans-retinoic acid) and Pharmacia Inc.'s Zinecard
Vesanoid is indicated for use in acute promyelocytic leukemia
(APL) in patients who relapse after an anthracycline regimen or
in those for whom standard regimens are contraindicated.
Although only a few patients in the Vesanoid studies were clearly
refractory to anthracycline-based induction regimens or showed
reasons why such therapy was contraindicated, these patients appeared
to respond at least as well as relapsed patients to Vesanoid therapy.
Therefore, the agent was also recommended for the treatment of
refractory patients, or those for whom anthracycline regimens
are not appropriate because of cardiomyopathy.
APL has a high early mortality rate. Ed Schnipper, MD, of Hoffmann-La
Roche, presented data from nonrandomized, uncontrolled studies
showing that Vesanoid has no appreciable effect on early death
from APL, but does improve long-term survival and strikingly decreases
At a Vesanoid dosage of 45 mg/m² for 90 days, the complete
response rate was 62% to 93%. Median survival was 11 months for
patients who had been in relapse. The time to complete remission
ranged from 40 to 90 days. The company recommends that patients
be placed on consolidation chemotherapy after 90 days of Vesanoid
treatment or when complete remission is achieved.
In APL patients who had been refractory to all types of chemotherapy
and in those for whom anthracyclines were contraindicated, treatment
with Vesanoid led to 1-year survival rates of 88% and 41%, respectively,
the company said.
Mortality from retinoic acid-APL syndrome (characterized by dyspnea,
fever, leukocytosis, pulmonary infiltrates, shivering, and renal
failure) had been high until the investigators discovered an effective
treatment--high doses of dexamethasone administered intravenously
for at least 3 days.