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Keywords:

  • purine analog;
  • chemoimmunotherapy;
  • follicular lymphoma;
  • mantle cell lymphoma;
  • marginal zone lymphoma;
  • Waldenstrom macroglobulinemia

Abstract

BACKGROUND

The combination of fludarabine, cyclophosphamide, and rituximab (FC-R) shows significant in vitro synergism and may improve patient outcome with little overlapping toxicity.

METHODS

Between December 2000 and June 2005, 77 patients completed therapy after a median of 4 cycles of FC-R (fludarabine at a dose of 25 mg/m2 intravenously [i.v.] on Days 1–3, cyclophosphamide at a dose of 250 mg/m2 i.v. on Days 1–3, and rituximab at a dose of 375 mg/m2 on Day 1). The median age of the patients was 59 years, 65% were male; 31% had previously untreated disease; and 44% had chronic lymphocytic leukemia (CLL), 29% had follicular lymphoma, and 27% other indolent lymphoid malignancies. In addition to standard disease response criteria, patients underwent evaluation using flow cytometric and/or molecular studies.

RESULTS

Objective responses (OR) and complete responses (CR) were observed in 83% and 42%, respectively, of evaluable patients (n = 76), respectively. For patients with CLL, the respective OR and CR rates were 100% and 67% as firstline therapy, and 95% and 14% as salvage therapy. For patients with follicular lymphoma, the respective OR and CR rates were 100% and 86% as firstline therapy, and 87% and 67% as salvage therapy. Responders who had no detectable disease on flow cytometric and/or molecular studies experienced prolonged remissions with no recurrences reported at a median 25 months of follow-up. Peripheral stem cell collection using stem cell factor plus granulocyte–colony-stimulating factor was successful in 10 of 13 patients who underwent mobilization (77%).

CONCLUSIONS

FC-R is highly active as initial or salvage therapy in patients with CLL or indolent non-Hodgkin lymphoma. Collection of autologous stem cells during molecular remission is feasible and may facilitate future exploration of high-dose therapy in these patients. Cancer 2006. © 2006 American Cancer Society.