Therapeutic Results from the Trials Managed by the French Cooperative Group on Chronic Lymphocytic Leukemia

Abstract

Since 1980, the French Cooperative Group on Chronic Lymphocytic Leukemia (CLL), including 43 hematological departments, has conducted three randomized clinical trials. More than 2,500 patients are nowadays randomized in these trials (973 in the CLL80 protocol and 1330 in the CLL85 protocol). These trials clearly contributed to the better knowledge and understanding of the CLL, in each stage of the disease.

In stage A-CLL, the protocol CLL80 included 611 patients, randomly allocated either to daily chlorambucil (n = 302) or abstention (n = 309). Results of the third interim analysis, based on the reference date of June 1, 1986, pointed out the complex action of chlorambucil, associating beneficial effects consisting in slowing down disease progression to stage B or C and favoring disease remission, with harmful effects given by a shorten survival and an excess of epithelial cancer, as compared with the no treatment group. However, the harmful effects of chlorambucil have not been yet observed in the CLL85 protocol, where 932 stages A were randomized between intermittent chlorambucil (n = 466) and no treatment (n = 466). Nevertheless, the potential harmful effects of the treatment raised out the question of therapeutical decision in stage A-CLL, and contributed to the design of the new protocol, CLL90, in which stage A-CLL are not treated until disease progression is observed.

In stage C-CLL, the CLL80 protocol included 70 patients. It demonstrated that the polychemotherapy CHOP, i.e. COP + doxorubicin improved these patients (n = 34) as compared with those treated with COP (n = 36), in terms of disease remission as well as survival. The CLL85 protocol involved 90 stages C, and showed no benefit on survival from methotrexate when associated with CHOP.

In stage B-CLL, the CLL80 protocol included 291 patients, who were randomized between daily chlorambucil (n = 150) and the COP polychemotherapy (n = 141). The interim analyses of this trial pointed out the closed results of these two treatments, either for disease remission or for survival. Thereafter, the protocol CLL85 randomized 287 stages B between two polychemotherapies, COP (n = 140) and CHOP (n = 147). However, although the follow-up of this latter trial is rather short considering the main endpoint (survival), no beneficial effect of the CHOP was observed in terms of overall survival, although a benefit was observed in terms of hematological response at the sixth month.

Considering the poor prognosis of the stages B and C, the current protocol (CLL90) compares, in both stages B and C, the effect of three treatments, namely CHOP, CAP and Fludarabine.

Key Words:

• CLL
• Controlled clinical trials
• (A, B, C) staging system