NEW YORK (Reuters Health) – As first-line treatment for progressive chronic lymphocytic leukemia (CLL), cladribine and fludarabine are equally effective and safe in combination with cyclophosphamide, according to phase III trial results.

Purine nucleoside analogs such as cladribine and fludarabine are among the most active drugs against CLL, hematologists in Poland note in the March 8 online issue of the Journal of Clinical Oncology. They had theorized that functional differences between the two agents would result in different treatment outcomes for CLL.

Indeed, they said, a 2007 interim report on a phase III trial comparing the two agents as monotherapy had found significantly higher complete response rates and longer progression-free survival in the cladribine arm.

In the current randomized multicenter trial, 192 subjects received cladribine, 0.12 mg/kg plus cyclophosphamide, 250 mg/m2 for 3 days, as first-line therapy. Another 203 received fludarabine, 25 mg/m2 plus the same dose of cyclophosphamide. Patients received up to 6 28-day cycles.

According to first author Dr. Tadeusz Robak, from the Medical University of Lodz, and colleagues, 47% in the cladribine group and 46% in the fludarabine group had complete responses, at a median follow-up of 3.2 years. The cladribine and fludarabine groups, respectively, had overall response rates of 88% and 82%, median progression-free survival of 2.34 years and 2.27 years, and estimated 4-year survival of 62.4% and 60.6%. None of these differences was statistically significant.

The investigators continued to see similar complete response rates when they stratified patients by demographic, clinical or cytogenetic factors.

Dr. Robak and colleagues can