title: Role of interferon alfa-2b in the induction and maintenance treatment of low-grade non-Hodgkin's lymphoma: results from a prospective, multicenter trial with double randomization.
abstract: OBJECTIVE
  To evaluate the effectiveness of adding interferon (IFN) alfa-2b to chemotherapy in the induction treatment of low-grade non-Hodgkin's lymphoma (NHL), and to assess the role of maintenance IFN.
  
  
  METHODS
  A multicenter, two-phase controlled trial with double randomization was conducted in 155 patients with low-grade NHL. In the first randomization, 78 patients received cyclophosphamide, vincristine, and prednisone (CVP) and IFN, 3 MU/m2 three times a week for 3 months, and 77 patients received CVP alone. Responding patients were randomized to receive IFN for 1 year versus observation.
  
  
  RESULTS
  Of 144 assessable patients, 73 received CVP + IFN and 71 received CVP. Responses were similar: CVP + IFN 79% versus CVP 76% (P = .62). The number of patients who did not complete the treatment was higher in the CVP + IFN group than in the CVP group (18% v 4%; P = .009), although the received dose-intensity of chemotherapy was comparable. Duration of response and progression-free survival (PFS) were significantly higher in the CVP + IFN group than in the CVP group (P = .0004). However, we observed no differences in overall survival (OS) (P = .30), with a median follow-up for the surviving patients of 3 years. Grade 3/4 granulocytopenia was the most frequent toxicity and was similar in both groups (33% v32%). Eighty-three (74%) of the 112 responding patients were randomized to maintenance IFN or observation. The duration of response was similar between 42 patients that received IFN compared with 41 control patients (P = .83), independently of treatment previously administered.
  
  
  CONCLUSIONS
  Adding IFN alfa-2b to induction CVP in low-grade NHL did not induce a higher response rate, but it significantly increased the duration of the responses. We found significant differences in PFS that favored the patients who received CVP + IFN, but not in OS. To date, no additional benefit has been seen from the administration of IFN for maintenance.
authors.affiliation: Haematology and Clinical Epidemiology Services, Hospital Universitario de la Princesa, Madrid, Spain. rarranzes@aehh.org
authors.forename: R
authors.initials: R
authors.lastname: Arranz
authors.forename: P
authors.initials: P
authors.lastname: García-Alfonso
authors.forename: P
authors.initials: P
authors.lastname: Sobrino
authors.forename: P
authors.initials: P
authors.lastname: Zamora
authors.forename: R
authors.initials: R
authors.lastname: Carrión
authors.forename: J
authors.initials: J
authors.lastname: García-Laraña
authors.forename: G
authors.initials: G
authors.lastname: Pérez
authors.forename: J
authors.initials: J
authors.lastname: López
authors.forename: E
authors.initials: E
authors.lastname: Lavilla
authors.forename: M
authors.initials: M
authors.lastname: Lozano
authors.forename: C
authors.initials: C
authors.lastname: Rayón
authors.forename: R
authors.initials: R
authors.lastname: Colomer
authors.forename: M G
authors.initials: MG
authors.lastname: Barón
authors.forename: E
authors.initials: E
authors.lastname: Flores
authors.forename: G
authors.initials: G
authors.lastname: Pérez-Manga
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Rañada
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011994:Recombinant Proteins; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone