Fludarabine 'Looks Like an Effective Treatment for CLL'

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[4970] Fludarabine Monophosphate as First Line Therapy for Chronic

Lymphocytic Leukemia (CLL) 11 Years Clinical Experience. Session

Type: Publication Only

J.E. Novoa, A.L. Rojo, B. Beñaran, R. Draper, H. Calvo, N. Iriondo,

L. , M. Rivero, A. Cabrera, M. Pebet, S. Brignoni, A. Luongo, R.

De Bellis (Intr. by Giralt) Hematology Service Angiogenesis

Center, FEMI COMERI. Police Hospital, Montevideo, Uruguay

Background: fludarabine (F) has become the standard first line

therapy for chronic lymphocytic leukemia (CLL) in younger patients.

Treatment of early stage patients with chlorambucil without risk

stratification has not been shown to prolong survival. In recent

years effective and potentially curative approaches such as

nucleosides analogues, stem cell transplantation or monoclonal

antibodies have been developed. The attraction of monoclonal

antibodies is based on selective targeting of tumor relevant surface

markers and a distinct mechanism of action (antibody-dependent

cellular cytotoxicity).

Aims: to assess the efficacy, safety and quality of life of F in

previously untreated B-cell CLL patients in a group of medical

institutions in Uruguay during 11 years (1995-2006).

Methods: 168 patients between the period 1995 2006 were

evaluated.120 of them received F intravenous formulation (1995-2006)

and 48 the oral one (2002-2006). Age: 48 85 years old, media 67

years old. Gender: male 90, female 78. Inclusion criteria for B-cell

CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old,

non multiorganic failure, performance status 0 2 (WHO), written

informed consent. First condition was non previous treatment.

Staging: Binet A 12/168, B 116/168 C 40/168. Treatment: as first

line therapy all the patients received (minimum): 6 cycles of i.v.

Fludarabine (Fludara, Schering) 25 mg/m2/daily (5 days) e/ 30 days or

Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles.

Results: on this B-cell CLL cohort the overall response rate (ORR)

was 78% (CR+PR), 80% of them have immunophenotypic response. Safety:

on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2

pancytopenia, 3 plaquetopenia. Grade 3-4 infection rate was 1,3%. No

alopecia was observed in any patient. Kaposi sarcoma (0,7%).

Mortality rate: 1,7% (3/168 patients). Other adverse factors to

overall survival were, age over 65 (p=0,0001) and hepatic impairment

(p=0,0001).

Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%,

infection 2%. Although fludarabine-treated patients experienced more

significant myelosuppression, no difference in the treatment group

was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated

disease 34%, second malignancy 17% and others 30%. Comparing oral

with intravenous formulation in overall survival the results were:

CLL 34% vs 36% (p= NS).

Conclusions: Fludarabine monofosfate (Fludara) looks like an

effective and safe treatment for B-cell CLL. The oral and intravenous

formulations have a similar response rate in elderly and young

patients. The challenge remains to integrate new information to apply

novel therapies in a disease-specific and risk-adapted maner. A

longer follow up and a larger trial, might be needed to confirm these

results.