High clinical and molecular response rates with fludarabine

Identifier:  imarina:9048168

Handle: https://hdl.handle.net/20.500.11797/imarina9048168

Authors:  Silvia Montoto Carol Moreno Eva Domingo-Doménech Cristina Estany Albert Oriol Albert Altés Joan Besalduch Carme Pedro Santiago Gardella Lourdes Escoda Antoni Asensio Pilar Vivancos Pilar Galán Alberto Fernández de Sevilla Josep M. Ribera Javier Briones Dolors Colomer Elías Campo Emili Montserrat Armando López-Guillermo

Abstract:
Purine analogs have demonstrated significant activity in patients with follicular lymphoma. The aim of this study was to analyze the efficacy and toxicity of a fludarabine combination as first-line treatment in patients with advanced-stage disease.Design and Methods This is a phase II trial including 120 patients (≤65 years) treated with 6 cycles of fludarabine, cyclophosphamide and mitoxantrone (FCM). Molecular response was assessed by q-PCR in peripheral blood.Results Of 119 patients with an assessable response, complete response was achieved in 99 (83%) partial response in 13 (11%) and 7 (6%) did not respond. After treatment, 37 out of 46 (81%) patients achieved molecular response. After a median follow-up of 3.9 years, 32 patients have relapsed. The 5-year progression-free survival was 58% (95% confidence interval: 47–69). Variables associated with a shorter progression-free survival were a poor performance status (ECOG≥2), ≥2 extranodal sites and high β2-microglobulin. Sixteen episodes of grade 3–4 infections were observed. Two patients died during therapy (of progressive multifocal leukoencephalopathy and bronchoaspiration respectively). No late toxicity has been observed. Twelve patients died during follow-up (9 after relapse, 2 during chemotherapy, 1 in complete remission after surgery for meningioma). The overall survival at 5 years was 89%. ECOG ≥2 and high β2-microglobulin were associated with a shorter survival.Conclusions FCM results in high complete and molecular response rates, with prolonged response duration in younger patients with advanced-stage follicular lymphoma. The combination of FCM with rituximab as front-line treatment warrants further investigation.