Role of Mitoxantrone in Combination Therapy for Chronic Lymphocytic Leukemia (CLL) Evaluated

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Role of Mitoxantrone in Combination Therapy for Chronic Lymphocytic Leukemia

(CLL) Evaluated

Researchers from Spain have reported preliminary results of initial treatment of

patients with chronic lymphocytic leukemia (CLL) with a combination of Rituxan®

(rituximab), Fludara® (fludarabine), Cytoxan® (cyclophosphamide) and Novantrone

(mitoxantrone) (R-FCM). However, researchers from the MD Cancer Center

question the utility of adding mitoxantrone to the combination Fludara, Cytoxan

and Rituxan (FCR) regimen. These two studies were presented at the 2007 annual

meeting of the American Society of Hematology.

Multiagent chemotherapy is the initial treatment of choice for high-risk younger

patients with CLL. However, there is still considerable debate over the optimal

treatment regimen.

The combination of Fludara, Cytoxan and mitoxantrone was a common regimen for

CLL prior to the use of Rituxan. Subsequent studies have shown that adding

Rituxan to this regimen improves outcomes of patients with CLL.

The study carried out by the Spanish Group for CLL evaluated 6 cycles of R-FCM

in 69 patients with untreated CLL.[1] All were under the age of 70 years and 85%

were Binet stage B or C. This regimen included Rituxan in induction and in

maintenance. Two thirds of the patients had an elevated LDH and beta-2

microglobulin. The overall response rate was 92%. The complete response rate was

74% and 37% of patients became PCR negative. They reported that diffuse marrow

involvement ZAP 70 and cytogenetics were not predictive of response. In the

maintenance phase of disease, some PCR negative patients became positive and

some positive patients became negative. There was one infectious death.

Researchers from the MD Cancer Center evaluated the importance of

mitoxantrone in combination with Fludara, Cytoxan and Rituxan.[2] The reviewed

data on FCR indicated a complete remission rate of 72% with complete molecular

remissions in 43%. This study included 30 patients with symptomatic CLL who had

a median age of 57 years and a maximum age of 69 years. Beta-2 microglobulin

levels were less than 4 mg/L and 13% were RAI stage III-IV. All were treated

with FCM-R with Neulasta® (pegfilgrastim) support. The overall response rate was

97%, the complete response rate was 80% and 65% of these patients had complete

molecular remissions. These data were compared to historical controls receiving

FCR and there were not differences between the two groups in response of time to

treatment failure. These authors concluded that FCM-R may not be better than

FCR. However, they reported that the tolerability of the two regimens was

equivalent.

Comments: These two studies suggest that FCMR is a very active regimen for the

treatment of symptomatic patients with CLL. A randomized trial would be

necessary to determine whether or not mitoxantrone improved outcomes.

Related News:

FCM-R Plus Neulasta® Highly Active in Previously Untreated CLL (06/15/2006)

Fludara®, Cyclophosphamide and Rituxan® Active in Early and Late CLL (6/24/2005

6:59:06 AM)

Addition of Rituxan® to Chemotherapy may be Superior to Chemotherapy Alone in

CLL (12/19/2003)

References

[1] Bosch F, Muntanola A, Villamor N, et al. Preliminary results of the

combination of rituximab, fludarabine, cyclophosphamide and mitoxantrone (R-FCM)

followed by rituximab maintenance in previosly untreated chronic lymphocytic

leukemia. Blood. 2007;110;193a, abstract 626.

[2] Faderl S, Wierda W, Ferrajoli A, et al. Update of experience with

fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline

therapy for chronic lymphocytic leukemia (CLL). Blood. 2007;110:193a, abstract

627.