title: Recombinant interferon-alpha2b added to oral cyclophosphamide either as induction or maintenance in treatment-naive follicular lymphoma: final analysis of CALGB 8691.
abstract: Recombinant interferon alpha-2b (IFN-alpha2) has direct and indirect antiproliferative effects in lymphoma, and may augment cytotoxicity when combined with chemotherapy. CALGB 8691 is a randomized study of daily oral cyclophosphamide (CPA) at 100 mg/m2 with or without IFN-alpha2 at 2 x 106 IU/m2 three times per week, followed by a second randomization between IFN-alpha2 maintenance (2 x 106 IU/m2 three times weekly) versus observation in treatment-naïve patients with follicular lymphoma (FL). Five hundred eighty-one patients were randomized to either CPA (n = 293) or CPA plus IFN-alpha2 (n = 288). One hundred five responding patients were randomized to observation and 99 to maintenance IFN-alpha2. With a median follow-up of 11.5 years, the median event-free and overall survival (OS) for CPA induction alone were 2.5 years (95% CI 2.2, 3.0) and 9 years (95% CI 7.7, 10.2), compared to 2.4 years (95% CI 2.1, 3.1) and 8.4 years (95% CI 7.5, 11.1) for the combination arm (p = NS). Patients with a partial response (PR) and randomized to observation had the worst outcome (event-free survival (EFS) 1.8 years versus 3.9 years; p = 0.002). Patients with a PR randomized to IFN-alpha2 had a similar EFS to compared to patients with complete response (CR), but this did not translate into a survival advantage. Myelosuppression was increased in IFN-alpha2-containing arms. Despite the small benefit in EFS in patients with PR randomized to IFN-alpha2 maintenance, we conclude that the addition of low dose IFN-alpha2 did not significantly improve the response rate, duration of response, event-free, or OS obtained with single-agent daily oral CPA in patients with previously untreated FL.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. smsmith@medicine.bsd.uchicago.edu
authors.forename: S M
authors.initials: SM
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: B D
authors.initials: BD
authors.lastname: Cheson
authors.forename: G
authors.initials: G
authors.lastname: Canellos
authors.forename: G
authors.initials: G
authors.lastname: Petroni
authors.forename: M
authors.initials: M
authors.lastname: Oken
authors.forename: D
authors.initials: D
authors.lastname: Duggan
authors.forename: D
authors.initials: D
authors.lastname: Hurd
authors.forename: J P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: B
authors.initials: B
authors.lastname: Parker
authors.forename: J
authors.initials: J
authors.lastname: Prchal
authors.forename: B A
authors.initials: BA
authors.lastname: Peterson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018951:Antigens, CD20 / Q000096:biosynthesis / Q000276:immunology; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D011994:Recombinant Proteins; D016019:Survival Analysis; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D018951:Antigens, CD20; D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003520:Cyclophosphamide