title: High clinical and molecular response rates with fludarabine, cyclophosphamide and mitoxantrone in previously untreated patients with advanced stage follicular lymphoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This is a phase II trial including 120 patients (< or =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> or =2), > or =2 extranodal sites and high beta2-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 > or =2 and high beta2-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.
authors.affiliation: Department of Hematology, Hospital Clínic, IDIBAPS, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.forename: Carol
authors.initials: C
authors.lastname: Moreno
authors.forename: Eva
authors.initials: E
authors.lastname: Domingo-Doménech
authors.forename: Cristina
authors.initials: C
authors.lastname: Estany
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.forename: Albert
authors.initials: A
authors.lastname: Altés
authors.forename: Joan
authors.initials: J
authors.lastname: Besalduch
authors.forename: Carme
authors.initials: C
authors.lastname: Pedro
authors.forename: Santiago
authors.initials: S
authors.lastname: Gardella
authors.forename: Lourdes
authors.initials: L
authors.lastname: Escoda
authors.forename: Antoni
authors.initials: A
authors.lastname: Asensio
authors.forename: Pilar
authors.initials: P
authors.lastname: Vivancos
authors.forename: Pilar
authors.initials: P
authors.lastname: Galán
authors.forename: Alberto Fernández
authors.initials: AF
authors.lastname: de Sevilla
authors.forename: Josep M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Javier
authors.initials: J
authors.lastname: Briones
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D012008:Recurrence; D015996:Survival Rate; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D001613:beta 2-Microglobulin / Q000096:biosynthesis
chemical_list: D001613:beta 2-Microglobulin; D003520:Cyclophosphamide; D008942:Mitoxantrone; D014740:Vidarabine; C024352:fludarabine