NUTLEY, NJ--Vesanoid (treti-noin, all-trans-retinoic acid) has become the first retinoid to receive a cancer treatment indication from the US Food and Drug Administration. The new agent, from Hoffmann-La Roche, is indicated for induction of remission in patients with acute promyelocytic leukemia (APL) who are refractory to or have relapsed from anthracycline chemotherapy, or for whom anthracy-cline chemotherapy is contraindicated.
Vesanoid is for induction of remission only, and it should be followed by an accepted form of remission consolidation and/or maintenance therapy.
In APL patients achieving complete remission, the agent produces an initial maturation of the primitive promye-locytes derived from the leukemic clone, followed by marrow repopulation by normal, polyclonal hematopoietic cells.
In an open-label, uncontrolled study from Memorial Sloan-Kettering Cancer Center and two cohorts of compassionate cases treated by multiple investigators under the auspices of the NCI, complete remissions among previously treated patients ranged from 50% to 80%, compared with rates of 30% to 50% previously reported for cytotoxic chemotherapy of APL in relapse.
Median survival for Vesanoid-treated patients ranged from 5.8 to 10.8 months, compared with less than 6 months in studies of cytotoxic chemotherapy.
In clinical trials, about 25% of Vesanoid-treated patients experienced retinoic acid-APL (RA-APL) syndrome, which is characterized by fever, dyspnea, weight gain, radiographic pulmonary infiltrates, and pleural or pericardial effusions. High-dose steroids given at the first suspicion of the syndrome appear to reduce morbidity and mortality.
During Vesanoid treatment, about 40% of patients will develop rapidly evolving leukocytosis. Patients who present with leukocytosis at diagnosis have an increased risk of a further rapid increase in WBC counts, which is associated with a higher risk of life-threatening complications. In these cases, adding full-dose chemotherapy to the Vesanoid regimen may be recommended.