Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma

• Published in: Journal of clinical oncology Vol. 24; no. 10; pp. 1590 - 1596
• Main Authors: HAGENBEEK, Anton, EGHBALI, Houchingue, TEODOROVIC, Ivana, NEGROUK, Anastassia, VAN GLABBEKE, Martine, MARCUS, Robert, MONFARDINI, Silvio, VITOLO, Umberto, HOSKIN, Peter J, DE WOLF-PEETERS, Christiane, MACLENNAN, Ken, STAAB-RENNER, Elvira, KALMUS, Joachim, SCHOTT, Astrid
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01.04.2006; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cyclophosphamide - therapeutic use; Female; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - drug therapy; Male; Medical sciences; Middle Aged; Neoplasm Staging; Prednisone - therapeutic use; Prospective Studies; Tumors; Vidarabine Phosphate - analogs & derivatives; Vidarabine Phosphate - therapeutic use; Vincristine - therapeutic use; Antineoplastic agent; Phase III trial; Phosphates; Early stage; Alkaloid; Cancerology; Lymphoproliferative syndrome; Malignant lymphoma; Advanced stage; Antimitotic; Low grade; Human; Corticosteroid; Purine nucleotide; Malignant hemopathy; Prednisone; Non Hodgkin lymphoma; Vincristine; Alkylating agent; Oxazaphosphinane derivatives; Chemotherapy; Cyclophosphamide; Fludarabine; Treatment; Antimetabolic; Nitrogen mustard; Adrenal hormone; Fluorine Organic compounds
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2005.03.7952

To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.