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.

DESIGN AND 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: 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, Grup per l'Estudi dels Limfomes de Catalunya I Balears (GELCAB) Spain
• Journal: Haematologica (Haematologica) Vol. 93 Issue 2 Pg. 207-14 (Feb 2008) ISSN: 1592-8721 [Electronic] Italy
• PMID: 18223288 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• beta 2-Microglobulin
• Cyclophosphamide
• Mitoxantrone
• Vidarabine
• fludarabine

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Humans
• Lymphoma, Follicular (drug therapy, metabolism, mortality)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage, adverse effects)
• Neoplasm Staging
• Recurrence
• Survival Rate
• Vidarabine (administration & dosage, adverse effects, analogs & derivatives)
• beta 2-Microglobulin (biosynthesis)