All-trans retinoic acid, low-dose cytosine arabinoside and granulocyte colony-stimulating factor in acute myelogenous leukemia: update of an illinois cancer center phase d pilot study

Thirty-nine pa with non-M3 acute myetoid leukemia (AML) (median age 65) received ATRA ISO mg/mVday (d) onlly, low-oose cylostoe anbinoside (LD Ari-C) 10 mg/m1 twice diily lubcutaneouily d 1-14 lad gnnulocyte cotony-ttimuJatinj factor (G-CSF) (FUgrutim) 5 fif/kf/d nbcuuneouly d 1-28 of ach 2S-d cycle. Pu had either rdipud from prior CR (11 pu), were refractory to prior therapy (11 p), had failed reinduction (3 pu), were previously untreated but had evolved from in antecedent myelodyiplattic syndrome (MDS) (5 pis) or had de amo AML and were older thin 70 yean (9 pts). Pu achieving CR received the identical program but every 6 weeks {or 1 year. Fifteen pts are inevatuaMe for response [11 received < 30 days of treatment due to toxicity (10) or progressive disease (1); 2 died prior to the first follow-up marrow; 2 were ineligible]. Grade m and IV nonbematologic toxichies included headache, hyperfailirubinemia and stomatitis in 4 pts each; pulmonary in 3 (1 dyspnea, 2 pulmonary infiltrates); nausea/email in 3; neurologic in 3 (2 fatigue/weakness, 1 lightheadedness); hypotension in 3; and elevated transaminases, cardiac (trial fibrillation with transient CHF), rash, infection, musculoskeletal pain, the 'stiff man syndrome in 1 pt each. Three pB developed leukocytosis (peak WBC 65.6, 84.0, 123xlOVL). Six (25%) of the 24 évaluable pts achieved CR, 4 (17%) partial remission (PR), 4 (17) stable disease and 10 (42%) progressive disease. Among the 14 previously untreated pts, 4 (29%) achieved CR, and 1 (7%) PR. Others (Vendtai, et il. Leukemia 9:1121, 1995) have reported similarly encouraging results. We conclude that this regimen can induce CR in pts with both previously mated and untreated AML, even in those with prior MDS with acceptable toxicity. The contribution of each agent and the precise mechanism by which remissions are induced remains to be determined.