Fludara and Cytoxan for Chronic Lymphocytic Leukemia – pro

Fludarabine is highly effective in the treatment of chronic lymphocytic leukemia, producing higher response rates than alkylating agents such as chlorambucil alone. Fludarabine is used in various combinations with cyclophosphamide, mitoxantrone, dexamethasone and rituximab in the treatment of indolent non-Hodgkins lymphomas and CLL.

According to an article published in The Lancet, the chemotherapy combination consisting of Fludara® (fludarabine) plus Cytoxan® (cyclophosphamide) significantly improves progression-free survival compared to Fludara alone without compromising quality of life in the treatment of chronic lymphocytic leukemia. The researchers concluded that the combination of Fludara plus Cytoxan “should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.”

This regimen is NCCN recommended.

To date, analysis of phase II data shows that fludarabine plus Rituxan® appear to be superior to fludarabine chemotherapy alone. This was confirmed by a recent Phase III trial in previously treated patients. Furthermore, fludarabine and cyclophosphamide plus Rituxan® improves survival over historical treatments including fludarabine plus or minus prednisone and fludarabine/cyclophosphamide. NCCN has now included the FCR regimen in its recommendations for patients less than 70 years of age. Accordingly, it has become standard for this disease.

Byrd JC, Rai KR, Peterson BL, Appelbaum FR, et al. The Addition of Rituximab to Fludarabine Significantly Improves Progression-Free and Overall Survival in Previously Untreated Chronic Lymphocytic Leukemia (CLL) Patients. Proc Am Soc Hem, Blood 2003; 102(11):73a, Abstract #245. Wierda W, O Brien S, Faderl S, Ferrajoli A, et al. Improved Survival in Patients with Relapsed -Refractory Chronic Lymphocytic Leukemia (CLL) Treated with Fludarabine, Cyclophosphamide, and Rituximab (FCR) Combination. Proc Am Soc Hem, Blood 2003; 102(11):110a, Abstract #373.

Rai KR et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000;343:1750-7.

Tournilhac O et al. Impact of frontline fludarabine and cyclophosphamide combined treatment on peripheral blood stem cell mobilization in B-cell chronic lymphocytic leukemia. Blood 2004;103:363-5.

Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. The Lancet. 2007;379: 230-239.

http://nccn.org/professionals/physician_gls/PDF/nhl.pdf, p.16

T. Robak, A. Dmoszynska, P. Solal-Celigny, K. Warzocha, J. Loscertales, J. Catalano, B. V. Afanasiev, L. Larratt, C. H. Geisler, M. Montillo, et al.
Rituximab Plus Fludarabine and Cyclophosphamide Prolongs Progression-Free Survival Compared With Fludarabine and Cyclophosphamide Alone in Previously Treated Chronic Lymphocytic Leukemia J. Clin. Oncol., April 1, 2010; 28(10): 1756 – 1765.

Nabhan C, Rosen ST, Chronic lymphocytic leukemia: a clinical review. JAMA. 2014 Dec 3;312(21):2265-76.

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