Bi-weekly chlorambucil treatment of chronic lymphocytic leukemia

Because the lymphocytes of chronic lymphocytic leukemia (CLL) are known to proliferate slowly, it was postulated that intermittent therapy might have a cumulative inhibitory effect on tumor cells while permitting normal cells to recuperate between doses. Sixty-two evaluable patients with CLL were treated with chlorambucil given orally as a single pulse every 2 weeks. The initial dose was 0.4 mg/kg; subsequent doses were increased by 0.1 mg/kg until toxicity or disease control was achieved. Responses were obtained in 6 of 8 (75%) previously untreated patients with indolent disease, in 18 of 31 (61%) previously untreated patients with active disease, in 7 of 14 (50%) previously treated patients not shown to be resistant to alkylating agents, and in 2 of 9 (22%) patients resistant to prolonged daily chlorambucil therapy. The over-all effectiveness in patients with CLL not previously resistant to chlorambucil was 31 of 53 (58%), with five complete remissions (9%). Hematologic toxicity was usually mild and never life-threatening. Gastrointestinal toxicity, which occurred in 23 of 62 patients, was usually mild and easily controlled with anti-emetics. It is concluded that bi-weekly oral administration of chlorambucil is effective therapy for CLL with response rates similar to daily continuous chlorambucil. Hematologic toxicity is considerably less than with daily treatment.