title: Adjuvant low-dose interleukin-2 (IL-2) plus interferon-α (IFN-α) in operable renal cell carcinoma (RCC): a phase III, randomized, multicentre trial of the Italian Oncology Group for Clinical Research (GOIRC).
abstract: There is currently no standard therapy to reduce the recurrence rate after surgery for renal cell carcinoma (RCC). The aim of this study was to assess efficacy and safety of adjuvant treatment with low doses of interleukin-2 (IL-2)+interferon-α (IFN-α) in operable RCC. The patients were randomized 1:1 to receive a 4-week cycle of low-dose IL-2+IFN-α or observation after primary surgery for RCC. Treatment cycles were repeated every 4 months for the first 2 years and every 6 months for the subsequent 3 years. The primary endpoint was recurrence-free survival (RFS); safety; and overall survival (OS) were secondary endpoints. ClinicalTrials.gov registration number was NCT00502034. 303/310 randomized patients (156 in the immunotherapy arm and 154 in the observation group) were evaluable at the intention-to-treat analyses. The 2 arms were well balanced. At a median follow-up of 52 months (range, 12-151 mo), RFS, and OS were similar, with an estimated hazard ratio (HR) of 0.84 [95% confidence interval (CI), 0.54-1.31; P=0.44] and of 1.07 (95% CI, 0.64-1.79; P=0.79), respectively in the 2 groups. Unplanned, subgroup analysis showed a positive effect of the treatment for patients with age 60 years and younger, pN0, tumor grades 1-2, and pT3a stage. Among patients with the combined presence of ≥ 2 of these factors, immunotherapy had a positive effect on RFS (HR=0.44; 95% CI, 0.24-0.82; P ≤ 0.01), whereas patients with <2 factors in the treatment arm exhibited a significant poorer OS (HR=2.27; 95% CI, 1.03-5.03 P=0.037). Toxicity of immunotherapy was mild and limited to World Health Organization grade 1-2 in most cases. Adjuvant immunotherapy with IL-2+IFN-α showed no RFS or OS improvement in RCC patients who underwent radical surgery. The results of subset analysis here presented are only hypothesis generating.
authors.affiliation: *Oncology Unit, Istituti Ospitalieri di Cremona, Cremona †Research and Innovation Unit ‡Medical Oncology Unit ¶Department of Clinical Medicine, Nephrology and Health Sciences, University Hospital of Parma, Parma §Medical Oncology Unit, IRCCS San Matteo University Hospital Foundation, Pavia ∥"Infrastructure Research and Statistics" Department, IRCCS-Arcispedale Santa Maria Nuova of Reggio Emilia, Reggio Emilia #Department of Oncology, Ospedali Riuniti di Bergamo, Bergamo **Oncology Unit, Arcispedale S. Maria Nuova di Reggio Emilia, Reggio Emilia ††Department of Oncology, University Hospital of Modena ‡‡Department of Oncology, Bolognini Hospital of Seriate, Alzano Lombardo §§Institute of Clinical Oncology, Carpi Hospital, Modena ∥∥Urology Unit, Vaio Hospital, Fidenza ¶¶Medical Oncology Unit, Hospital of Guastalla, Guastalla, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Passalacqua
authors.forename: Caterina
authors.initials: C
authors.lastname: Caminiti
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
authors.forename: Luca
authors.initials: L
authors.lastname: Braglia
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.forename: Augusto
authors.initials: A
authors.lastname: Vaglio
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Ermanno
authors.initials: E
authors.lastname: Rondini
authors.forename: Roberto
authors.initials: R
authors.lastname: Sabbatini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nastasi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Artioli
authors.forename: Andrea
authors.initials: A
authors.lastname: Prati
authors.forename: Michele
authors.initials: M
authors.lastname: Potenzoni
authors.forename: Debora
authors.initials: D
authors.lastname: Pezzuolo
authors.forename: Elena
authors.initials: E
authors.lastname: Oliva
authors.forename: Federico
authors.initials: F
authors.lastname: Alberici
authors.forename: Carlo
authors.initials: C
authors.lastname: Buzio
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000276:Adjuvants, Immunologic; D016898:Interferon-alpha; D007376:Interleukin-2