Higher Chronic Lymphocytic Leukemia Remissions with Fludarabine
Patients given fludarabine as the first treatment for chronic lymphocytic leukemia (CLL) have higher clinical remission rates and longer remissions as compared with two other treatments, according to a study from the French Cooperative Group on CLL. The study -- an international, multicenter clinical trial involving 938 patients -- was published in the journal Blood on October 15, 2001, and compared three different treatments as initial therapy for high- and intermediate-risk CLL (see the journal abstract).
Patients treated with fludarabine had higher remission rates and experienced less frequent and severe side effects of chemotherapy than patients who received either of two multidrug treatment regimens. In addition, patients receiving fludarabine who achieved partial or complete remission were able to delay further treatment for 13 to 20 months longer than patients on the other drug regimens.
However, fludarabine offered no survival advantage -- five-year survival was similar in the three groups of patients.
Patients enrolled in the study had untreated CLL with swollen lymph nodes, anemia, or other signs indicating the spread of leukemic cells to other parts of the body. They were randomly assigned to receive one of three treatments: fludarabine, CAP or ChOP. CAP is a three-drug regimen including cyclophosphamide, Adriamycin (doxorubicin) and prednisone. ChOP is a four-drug regimen including cyclophosphamide, Oncovin (vincristine), prednisone and doxorubicin.
“Fludarabine is not a curative agent for CLL,” conclude principal investigator Michel Leporrier and his colleagues from the French Cooperative Group on CLL. “Nevertheless…fludarabine displays some advantages, including improved tolerance, higher clinical remission rate and delayed time to retreatment, which can argue for the choice of this drug as a front-line treatment in patients with previously untreated advanced CLL.”
Clinical remission occurred in 40 percent of patients treated with fludarabine, compared with 30 percent of patients treated with ChOP and 15 percent of patients treated with CAP. Although the length of time until the CLL became active again was no different among the three treatment groups, patients who received fludarabine did not require further treatment for 45 months on average. By contrast, patients treated with the ChOP and CAP regimens required further treatment after 32 months and 26 months, respectively.
Patients who received CAP and ChOP suffered from nausea, vomiting and hair loss more frequently and severely than did patients treated with fludarabine. Low blood counts were the most common side effect of treatment in patients who received fludarabine.
Despite the differences in remission rates, average and five-year survival were almost identical in the three groups of patients. Patients treated with fludarabine survived an average of 69 months, those who received the ChOP regimen 67 months, and those who received the CAP regimen 70 months. Among patients treated with fludarabine, 58 percent survived for five years, compared with 57 percent of patients treated with the ChOP regimen and 60 percent of patients receiving the CAP regimen.
These results support the findings of a United States multicenter trial reported in December 2000 in the New England Journal of Medicine. In that trial, although fludarabine did not improve overall survival, it yielded a higher response rate and a longer duration of remission than chlorambucil, which was long considered the standard initial therapy for CLL in the United States.
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