The Eastern Cooperative Oncology Group (ECOG) conducted a study in which patients with advanced chronic lymphocytic leukemia (CLL) were randomized between a regimen consisting of chlorambucil (30 mg/m2 orally day 1) and prednisone (80 mg orally days 1 to 5) (C + P) administered every 2 weeks and a more intensive regimen of cyclosphosphamide (300 mg/m2 orally days 1 to 5), vincristine (1.4 mg/m2 intravenously [IV] day 1), and prednisone (100 mg/m2 orally days 1 to 5) (CVP) given every 3 weeks. Treatment was continued for up to 18 months to maximal response. Of the 122 eligible patients, 60 received C + P, while 62 received CVP. With a median follow-up of 7 years, there were no significant differences in survival (4.8 v 3.9 years, P = .12), complete remission (CR) rate (25% v 23%; P = .83), or duration of response (2.0 v 1.9 years; P = .78) between C + P and CVP. Toxicity was modest despite the prolonged treatment. The long median survival of 4.1 years for stage III and IV patients is superior to that usually reported. This could stem from continuing treatment to maximal response rather than an increase in intensity of therapy. These results are comparable to those reported with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy by other investigators. The data suggest that intermittent C + P administered to maximal response continues to be the standard treatment approach for advanced CLL.
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.
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