Rituximab in combination with fludarabine and cyclophosphamide in the treatment of patients with recurrent follicular lymphoma.
BACKGROUND
The current study was conducted to asses the safety profile and clinical activity of rituximab in combination with fludarabine and cyclophosphamide in patients with recurrent follicular lymphoma (FL).


METHODS
This study was a noncomparative, multicenter, phase II study. Between March 2000 and December 2002, 54 patients with recurrent FL were enrolled in the FC+R trial. Patients received fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 300 mg/m(2) daily for 3 consecutive days, every 3 weeks for 4 cycles. Rituximab was administered at a dose of 375 mg/m(2) beginning 2 weeks after the first course of fludarabine and cyclophosphamide and then on Day 1 of each cycle thereafter. The planned treatment duration was 10 weeks.


RESULTS
Overall, 92% of patients completed the planned therapy in 10 to 14 weeks and 74% achieved a complete response (CR). Among patients with BCL2-positive bone marrow, 86% obtained a molecular disease remission (MR). The median survival from treatment (SFT), the duration of disease remission (DR), and time to disease progression (TTP) had not been reached after a median follow-up of 45 months. Of the baseline characteristics, >2 previous treatments, BCL2-positive bone marrow, and low Follicular Lymphoma International Prognostic Index (FLIPI) score were found to be associated with better DR and/or TTP. Hematologic toxicity was transient and reversible, with the exception of 3 patients with severe and prolonged neutropenia. Three patients presented with infections, 1 of whom died of bronchopneumonia.


CONCLUSIONS
The FC+R scheme, a nonanthracycline-containing regimen lasting up to 10 weeks, was found to be relatively well-tolerated and demonstrated significant antilymphoma activity with excellent clinical CR and molecular response rates.
Sacchi
Stefano
S
Department of Oncology and Hematology, University of Modena, Modena, Italy. ssacchi@unimo.it
Pozzi
Samantha
S
Marcheselli
Raffaella
R
Federico
Massimo
M
Tucci
Alessandra
A
Merli
Francesco
F
Orsucci
Loretta
L
Liberati
Marina
M
Vallisa
Daniele
D
Brugiatelli
Maura
M
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009503:Neutropenia / Q000139:chemically induced; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D000069283:Rituximab; D013921:Thrombocytopenia / Q000139:chemically induced; D013997:Time Factors; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019253:Proto-Oncogene Proteins c-bcl-2; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine