INDUCTION REGIMEN FOR OLD AML PATIENTS

Adding Cytarabine to Clofarabine Induction Improves Response Rate in AML

NEW YORK (Reuters Health) Oct 10 - Clofarabine plus low-dose cytarabine achieves better response rates than clofarabine alone when used as front-line therapy for older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), according to a report in the September 1st issue of the journal Blood.

"There are clear limits in the efficacy of standard induction therapy for elderly patients with AML, and much more research is needed," Dr. Stefan Faderl from the University of Texas M. D. Anderson Cancer Center in Houston told Reuters Health. "Clofarabine is only one example in this direction."

In 70 previously untreated patients aged 60 years or older with AML or high-risk MDS, Dr. Faderl and colleagues studied the effects of clofarabine 30 mg/m daily for 5 days with or without cytarabine 20 mg/m daily for 14 days.

Thirty-nine patients (56%) achieved complete remission, the authors report.

Complete remission and overall response rates were 63% and 67%, respectively, with the clofarabine-cytarabine combination, vs 31% and 31%, respectively, with clofarabine alone.

Response rates declined continuously with age, falling from 80% in patients 60 to 64 years old to 40% in those older than 70 years, the researchers note.

Toxicity was comparable for the 2 regimens, the report indicates.

Median event-free survival was significantly longer for patients on the combination (7.1 months) than for those on clofarabine-only (1.7 months), the investigators say, but median overall survival, median remission duration, and median survival of complete responders did not differ significantly between the groups.

"Although patients on the combination arm benefited with respect to better event-free survival, long-term outcome remains unsatisfying," the researchers write.

"We are still interested in the clofarabine/cytarabine combination," Dr. Faderl said. "A follow up study will contain the combination followed by a longer consolidation including hypomethylator drugs. There is also still room for thoughts about changes in doses and schedules."

"There is no single one preferred regimen (for AML in the elderly), as none of them has established itself clearly over others," Dr. Faderl concluded. "There remains room for a number of ideas and drugs in this particular area."

Blood 2008;112:1638-1645.