Fludarabine/cyclophosphamide/rituximab successful against CLL

NEW YORK (Reuters Health) - Sequential therapy using fludarabine, high-dose cyclophosphamide and rituximab produces high-quality responses in previously untreated patients with chronic lymphocytic leukemia (CLL), according to researchers at Memorial Sloan-Kettering Cancer Center in New York.

In the Journal of Clinical Oncology published online on December 15 ahead of print, Dr. Mark A. Weiss and colleagues report that 89% of the assessable patients in the trial experienced a response, and 61% experienced a complete response (CR).

The study is an extension of earlier work by these researchers, in which they compared therapy with fludarabine alone versus fludarabine as induction therapy followed by consolidation with high-dose cyclophosphamide. This earlier trial, reported in 2000, found that sequential therapy markedly improved the frequency of CR, from 8% using single-agent fludarabine, to 38%.

For the current study, 39 patients were enrolled between September 1998 and September 2004. All received induction with fludarabine 25 mg/m�/d intravenously for 5 days every 4 weeks. Patients with no response after 3 such cycles moved directly to intravenous cyclophosphamide, 3,000 mg/m� every 3 weeks for 3 doses. All other patients received 6 cycles of fludarabine and 4 to 6 weeks later went on to cyclophosphamide. Approximately 4 weeks after completing cyclophosphamide, participants began receiving the second consolidation: rituximab 375 mg/m� once weekly for 4 doses.

Response evaluations were done at baseline, before the 4th cycle of fludarabine, before the start of cyclophosphamide, before the start of rituximab, and 4 to 6 weeks after completion of rituximab. The median follow-up interval was 60 months. Three patients of the original 39 withdrew from the trial before beginning cyclophosphamide. Of the 36 assessable patients, 14 had intermediate-risk disease, and 22 had high-risk disease.

After completing fludarabine, four patients (11%) achieved a CR, but after the cyclophosphamide consolidation, 14 patients (39%) had a CR and 22 patients had lesser responses. Of these 22, eight with partial responses achieved a CR when consolidated with rituximab. The median response duration was 43 months.

The actuarial survival rate at 5 years was 92% for patients experiencing either CR or nodular partial response, versus 33% for other patients. In addition, the quality of response was found to be a better predictor of overall survival than was baseline stage of disease.

There were no treatment-related deaths or early withdrawals. Grade 3 or 4 anemia occurred in six patients, neutropenia in 32, and thrombocytopenia in 28.

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