Combined Chemotherapy Improves CLL Outcomes but Not Survival

SUTTON, England, July 20 -- Progression-free survival in chronic lymphocytic leukemia was extended significantly over monotherapy by combining fludarabine and cyclophosphamide, found an international study.

But five-year overall survival with the combination over fludarabine or chlorambucil monotherapy did not improve, Daniel Catovsky, M.D., of the Institute of Cancer Research here, and collaborators, in eight countries reported in the July 21 issue of The Lancet. The complete response rate was also significantly improved.

In a multicenter trial, five-year progression-free survival was 36% with the combination versus 10% for fludarabine or chlorambucil alone (P=0.00005), the investigators found.

The chemotherapy doublet led to complete responses in 38% of patients, more than double the number with fludarabine alone (P

After a median follow up of 41 months the overall response rate with the combination therapy was 94% compared with 80% for fludarabine alone (P

The results of this trial and of the meta-analysis should not be interpreted as showing that treatment had no impact on survival, Drs. Shanafelt and Kay continued.

"[A] reasonable interpretation of the randomized trials for patients with CLL is that the sequence of treatment might not affect survival if all treatment options are available to patients with progressive disease as a salvage therapy," they wrote. "Indeed this trial provides additional evidence that response to second-line therapy confounds interpretation of overall survival in trials of first-line therapy for patients with CLL."