Fludarabine versus chlorambucil: is the debate over?

Historically, chlorambucil had been considered to be the treatment of choice for previously untreated patients with chronic lymphocytic leukemia (CLL) from the 1950's until 1990's. Ever since the 1990's, when the nucleoside analogue, fludarabine, became available as a therapeutic agent, this drug has replaced chlorambucil in the treatment of CLL. In the initial treatment of CLL. Although, prospectively conducted, randomized clinical trials comparing these two drugs in the front-line therapy of CLL, initially, showed a significant increase in the complete remission rates, overall remission rates, and progression-free-survival in patients treated with fludarabine, as compared to the patients treated with chlorambucil, the overall survival duration did not show a significant improvement improvement. A recent report, of a long-term follow-up of that study now reveals that a significant increase in the overall survival time of the patients who, originally, were randomized to fludarabine arm started to become manifest only after about 6 years had passed from the time of first treatment on this study. Thus, fludarabine has now been proven to be superior to chlorambucil for the initial treatment of CLL.