Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma.

Abstract

PURPOSE:

Promising new therapeutic options for follicular lymphoma (FL) include fludarabine plus mitoxantrone (FM) and the mouse/human anti-CD20 antibody, rituximab. We performed a randomized comparative trial of FM with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) front-line chemotherapy with and without sequential rituximab.

PATIENTS AND METHODS:

All previously untreated CD20(+) FL patients presenting in 15 Italian cooperative institutions from October 1999 were randomly allocated to FM or CHOP. Following clinical or molecular restaging, patients in complete remission (CR) with bcl-2/IgH negativity (CR(-)) received no further treatment; those in CR with bcl-2/IgH positivity (CR(+)) received rituximab, as did those in partial remission (PR) with bcl-2/IgH negativity (PR(-)) or positivity (PR(+)); nonresponders (NR subgroup) were off study.

RESULTS:

After chemotherapy, the FM arm achieved higher rates of CR (68% [49 of 72 patients] v 42% [29 of 68 patients]; P =.003) and CR(-) (39% [28 of 72 patients] v 13 of 68 patients [19%]; P =.001). Rituximab elicited CR(-) in 55 of 95 treated patients (58%). The final CR(-) rate was higher in the FM arm (71% [51 of 72 patients] v 51% [35 of 68 patients]; P =.01). However, with a median follow-up of 19 months (range, 9 to 37 months), no statistically significant difference was found among the various study arms in terms of both progression-free (PFS) and overall survival (OS).

CONCLUSION:

These results indicate that FM is superior to CHOP for front-line treatment of FL and that rituximab is an effective sequential treatment option. However, they also confirm that this superiority is unlikely to translate into either better PFS or OS.

• Authors: Pier Luigi Zinzani, Alessandro Pulsoni, Alessio Perrotti, Simona Soverini, Francesco Zaja, Amalia De Renzo, Sergio Storti, Vito Michele Lauta, Luciano Guardigni, Patrizia Gentilini, Alessandra Tucci, Anna Lia Molinari, Marco Gobbi, Brunangelo Falini, Pier Paolo Fattori, Fabrizio Ciccone, Lapo Alinari, Maurizio Martelli, Stefano Pileri, Sante Tura, Michele Baccarani
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 13 Pg. 2654-61 (Jul 01 2004) ISSN: 0732-183X [Print] United States
• PMID: 15159414 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Rituximab
• Vincristine
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Administration, Oral
• Adult
• Aged
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Female
• Humans
• Infusions, Intravenous
• Lymphoma, Follicular (drug therapy, pathology)
• Male
• Middle Aged
• Prednisone (administration & dosage)
• Rituximab
• Treatment Outcome
• Vincristine (administration & dosage)