Fludarabine and mitoxantrone for patients with chronic lymphocytic leukemia

BACKGROUND. The objective of the current study was to assess the efficacy of combination therapy with fludarabine and mitoxantrone in patients with B-cell chronic lymphocytic leukemia (CLL). METHODS. Eighty-eight patients were treated with fludarabine 30 mg/m² intravenously daily for 3 days and mitoxantrone 10 mg/m² on Day 1 (FN). Patients were divided into four groups based on expected response to single-agent fludarabine. These four groups included previously untreated patients, patients who previously were treated with alkylating agents, patients who were successfully treated with alkylating agents and fludarabine but who developed recurrent disease, and patients whose disease was refractory to fludarabine with or without alkylating agents. RESULTS. The overall response rate was 66%. The response rates were 83% in previously untreated patients, 87% in patients previously treated with alkylating agents, 50% in patients whose disease was not refractory to fludarabine at the start of therapy, and 25% in patients whose disease was refractory to fludarabine. The complete remission (CR) rate was 20% for previously untreated patients, which was not significantly different from the CR rate for a group of historical control patients who were treated with single-agent fludarabine. The median follow-up was 8 years for surviving patients. The median progression free survival was 24 months for all patients and 34 months for previously untreated patients. The median overall survival was 40 months, and the median survival of previously untreated patients was 88 months. The most common toxicities were myelosuppression and infection. Eleven patients (12.5%) developed a second malignancy after a median of 62 months. CONCLUSIONS. The FN regimen did not have a significant advantage over fludarabine alone in the treatment of patients with CLL.