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 (dexrazoxane for injection).
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 early morbidity.
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(Drug information on dexamethasone) administered intravenously for at least 3 days.