SEATTLE--Fludarabine (Fludara) has demonstrated impressive results in previously untreated patients with active chronic lymphocytic leukemia (CLL) when compared with chlorambucil(Drug information on chlorambucil) (Leukeran), Kanti Rai, MD, said at the American Society of Hematology (ASH) annual meeting.
"Chlorambucil has been the gold standard treatment for CLL," said Dr. Rai, chief of the Department of Hematology and Oncology, Long Island Jewish Hospital, New Hyde Park, NY. Although chlorambucil produces response rates of up to 60% to 70%, the great majority are partial, not complete, responses. "Overall, the natural history of CLL has not been shown to be altered or improved by any treatment, and nothing we did was improving survival," he said.
Fludarabine is currently indicated for the treatment of patients with B-cell CLL who have not responded to, or whose disease has progressed during, treatment with a regimen containing at least one standard alkylating agent. A study from M.D. Anderson showed that fludarabine was significantly more effective in previously untreated patients with active disease, compared with other drugs.
This finding prompted the randomized intergroup study in previously untreated CLL patients with active disease, Dr. Rai said. The study involved the Cancer and Leukemia Group B (CALGB), Southwest Oncology Group (SWOG), National Cancer Institute (NCI), Clinical Trial Group of the NCI of Canada, and the Eastern Cooperative Oncology Group (ECOG).
Over a period of 3½ years (October 1990 through April 1994), more than 450 intermediate-risk and high-risk patients were randomized to receive either flu-darabine, 25 mg/m² by ½-hour intravenous infusion daily from days 1 to 5 every 4 weeks, or chlorambucil, 40 mg/m² by mouth on day 1 every 4 weeks.
Initially, a third randomized arm combined the two drugs but was closed when an interim analysis showed unacceptably high hematologic toxicity and a response rate no better than that achieved by fludarabine alone, Dr. Rai said.
The study, with a primary endpoint of complete remission, was comprised of two phases: Patients showing continued beneficial response received the assigned therapy for a maximum of 12 months, and nonresponding patients and those relapsing within 6 months were crossed over to the alternate therapy.