Vesanoid, First Retinoid to Receive a Cancer Indication,Is Approved for Treatment of APL

NUTLEY, NJ--Vesanoid (treti-noin, all-trans-retinoic acid) hasbecome the first retinoid to receive a cancer treatment indicationfrom the US Food and Drug Administration. The new agent, fromHoffmann-La Roche, is indicated for induction of remission inpatients with acute promyelocytic leukemia (APL) who are refractoryto or have relapsed from anthracycline chemotherapy, or for whomanthracy-cline chemotherapy is contraindicated.

Vesanoid is for induction of remission only, and it should befollowed by an accepted form of remission consolidation and/ormaintenance therapy.

In APL patients achieving complete remission, the agent producesan initial maturation of the primitive promye-locytes derivedfrom the leukemic clone, followed by marrow repopulation by normal,polyclonal hematopoietic cells.

In an open-label, uncontrolled study from Memorial Sloan-KetteringCancer Center and two cohorts of compassionate cases treated bymultiple investigators under the auspices of the NCI, completeremissions among previously treated patients ranged from 50% to80%, compared with rates of 30% to 50% previously reported forcytotoxic chemotherapy of APL in relapse.

Median survival for Vesanoid-treated patients ranged from 5.8to 10.8 months, compared with less than 6 months in studies ofcytotoxic chemotherapy.

In clinical trials, about 25% of Vesanoid-treated patients experiencedretinoic acid-APL (RA-APL) syndrome, which is characterized byfever, dyspnea, weight gain, radiographic pulmonary infiltrates,and pleural or pericardial effusions. High-dose steroids givenat the first suspicion of the syndrome appear to reduce morbidityand mortality.

During Vesanoid treatment, about 40% of patients will developrapidly evolving leukocytosis. Patients who present with leukocytosisat diagnosis have an increased risk of a further rapid increasein WBC counts, which is associated with a higher risk of life-threateningcomplications. In these cases, adding full-dose chemotherapy tothe Vesanoid regimen may be recommended.

Vesanoid is teratogenic, and adequate contraception is essentialfor women of childbearing potential.