title: Phase II study of fludarabine combined with interferon-alpha-2a followed by maintenance therapy with interferon-alpha-2a in patients with low-grade non-hodgkin's lymphoma.
abstract: Randomized trials suggest improved disease-free survival in low-grade non-Hodgkin's lymphoma (LGNHL) when interferon is combined with multiagent chemotherapy. This phase II trial was conducted to investigate the feasibility of combining fludarabine monophosphate (fludarabine) and IFN in a regimen for treatment of LGNHL. Twenty-one patients were evaluable. Median age was 55 years, and patients had been treated with an average of 1.7 chemotherapy regimens before enrollment. Patients received 25 mg/m2 of fludarabine intravenously on days 1 through 5 followed by 2 x 10(6) U/m2 of interferon-alpha-2a subcutaneously on days 22 through 26. Cycles were repeated every 4 weeks with delays and dose modifications for significant cytopenias. Patients were restaged after cycles 4 and 8, and those with at least a partial response to therapy were given maintenance therapy consisting of 2 x 10(6) U/m2 interferon-alpha-2a subcutaneously three times per week for 6 months. The overall response rate was 76% with a 25% complete response (CR) rate. Overall response rates were 75% (3/4 with 2 CR's) for chemotherapy-naive patients and 76% (13/17 with 3 CR's) for previously treated patients. Median time to progression was 12 months, and currently two patients are without evidence of progression at a median follow-up of 55 months. Grade III or greater toxicities included neutropenia (39%), anemia (17%), thrombocytopenia (5%), fevers/chills (5%), and fatigue (5%). Fludarabine and interferon can be effectively and safely combined in a regimen with significant activity against LGNHL. A modification of this regimen may be suitable for further study.
authors.affiliation: Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida 32610, U.S.A.
authors.forename: James W
authors.initials: JW
authors.lastname: Lynch
authors.forename: David L
authors.initials: DL
authors.lastname: Hei
authors.forename: Raul C
authors.initials: RC
authors.lastname: Braylan
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimzsa
authors.forename: Edward V
authors.initials: EV
authors.lastname: Staab
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Bewsher
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
authors.forename: John K
authors.initials: JK
authors.lastname: Hudson
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008875:Middle Aged; D011994:Recombinant Proteins; D012074:Remission Induction; D001084:Vidarabine Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D001084:Vidarabine Phosphate; C042382:fludarabine phosphate