Prolonged Administration of Arsenic Trioxide (Trisenox®) for Patients with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) at MD Anderson Cancer Center: A Phase II Study.

The value of prolonged administration of arsenic trioxide (ATO) was examined in patients (pts) with MDS and CMML. ATO (0.25 mg/kg) was given intravenously over 1 hour daily for five days followed by 0.25 mg/kg twice weekly for 11 weeks. Pts were assessed at 4 weeks, at the end of the first course, and then monthly. Pts with stable disease were eligible for further courses. The study included 14 RBC transfusion-dependent MDS pts (6 RA/RARS, 8 RAEB; 12 IPSS risk Low/Int1, 2 Int2/High), and 3 CMML pts. Median age was 67 years (range 46–84). Six pts had a history of previous treatment other than supportive care. 16 pts were evaluable for toxicity and response. One pt received 3 courses, 3 received 2 courses, and 13 received 1 course. Hematologic responses (IWG criteria) were observed in 4 pts (25%) and 9 (6 MDS,3 CMML) had stable disease:

Hematologic/cytogenetic CR was achieved in one pt: a 76 year old male, RAEB-2, Int 2, complex chromosomal abnormalities, who had previously failed thalidomide for 6 months and thalidomide + cyclosporin A for 3 months. Of the 3 CMML pts, one had transient reduction of absolute monocyte counts during each of 2 courses; all 3 had stable disease. In 24 courses there were 6 febrile episodes in 4 patients, requiring admission, all in pts with pre-existing neutropenia; 1 Grade 3 and 1 Grade 4 thrombocytopenia, 1 Grade 3 neutropenia, all requiring dose modification; 1 episode of accelerated functional cardiac rhythm; and 1 anemia-precipitated congestive heart failure, which was unlikely related to the drug. There were 22 episodes of Grade 1 or 2 drug-related toxicities. Four responses of 3–7+ mo. duration were observed, including 1 CR, suggesting activity in an as yet undefined subgroup of MDS pts. No benefit of prolonged treatment was documented. ATO was safe in this outpatient setting for elderly patients. Observed low toxicity and documented activity support future trials of ATO in combination with other agents in treatment of MDS.