Fludarabine Monophosphate in Indolent Non Hodgkin’s Lymphoma (NHL) - Clinical Experience (1995–2006).

Background: fludarabine (F) is licensed for the management of indolent non Hodgkin’s lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of NHL achieving objective response rates. The non Hodgkin’s lymphomas are a heterogeneous group of lymphomas involving predominantly malignant populations of B lymphocytes, although T or natural killer type (NK) may be present.

Aims: to assess the efficacy, safety and quality of life of F in previously untreated indolent NHL in a Group of Medical Institutions in Uruguay during 11 years (1995–2006).

Methods: 98 patients between the period 1995 – 2006 were evaluated. 72 of them received the intravenous formulation (1995–2006) and 26 the oral one (2002–2006).

Age: 38 – 85 years old, media 58 years old.

Gender: male 52% & female 48%. Inclusion criteria for NHL-LG was: non previous treatment, Ann Arbor stage III or IV (nodal or extradonal), a meassurable mass, age > 18 years old, WHO performance status 0–2 and written informed consent. WHO performance status 0: 60 pts, 1: 24 pts and 2: 14 patients. Ann Arbor staging: IIIA:16/98 IIIB:9/98 IVA:51/98 and 22 IVB. Treatment: 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 NHL-LG cohort the overall response rate (PR+CR) was 78% (ORR), 44% complete response and 34% partial response. Stable disease 2%. Progressive disease 23%. Time to progression 15 months. Overall survival at 60 months was 68%. LDH in serum was an adverse prognostic factor for time to progression and overall survival.

Safety: on the 622 cycles in 98 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 1 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient.

Mortality rate: 1,02% (1/98 patients). Other adverse factors to overall survival were, age over 65 years old (p=0,0001) and hepatic impairment (p=0,0001).

Toxicity: (WHO>2): granulocytopenia 18%, thrombocytopenia 10%, infection 6%. Although fludarabine-treated patients experienced more significant myelossuppresion, no difference in the treatment group was demonstrated. Causes of death: sepsis 10%, associated disease 46%, second malignancy 7% and others 37%. Comparing oral with intravenous formulation in overall survival the results were: NHL-LG 77% vs 73% (p= NS).

Conclusions: fludarabine monofosfate (Fludara®) is an effective and safe treatment for NHL-LG. The oral and intravenous formulations have a similar response rate in elderly and young patients. A longer follow up and a larger trial, might be needed to confirm these results in a multicenter, randomized study.