title: Phase II randomized study of interleukin-2 with or without 13-cis retinoic acid as maintenance therapy in patients with advanced cancer responsive to chemotherapy.
abstract: OBJECTIVE
  In a previous phase 1B study, we determined the optimal biological dose of interleukin-2 (IL-2) and 13-cis retinoic acid (RA), given as maintenance therapy to patients with a variety of solid tumors, responding to chemotherapy, with a high risk of relapse. This therapy produced a statistically significant increase of the CD4+/CD8+ ratio, natural killer (NK) and lymphocyte cell counts and a decrease of vascular endothelial growth factor (VEGF). The aim of this phase II randomized study was to verify the role of RA in this drug combination.
  
  
  METHODS
  One hundred and twelve patients, with locally advanced or metastatic tumors responding to chemotherapy, were randomized to receive IL-2, 1.8 x 10(6) I.U. for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week interval (arm A), or the same regimen plus oral RA, 0.5 mg/Kg (arm B). VEGF, the CD4+/CD8+ ratio, NK and tumor markers were assessed every 2 months and response every 4 months.
  
  
  RESULTS
  The baseline characteristics were well balanced between the two treatment arms for age, performance status, type of disease, amount of previous chemotherapy and baseline values of NK, CD4+/CD8+ and VEGF. Toxicity was minor in both arms. After a median follow-up of 42 months, all immunological parameters improved in both arms with respect to the baseline values; this improvement was statistically more significant in arm B. There was no statistically significant difference in progression-free and in overall survival between the two arms.
  
  
  CONCLUSIONS
  These data show that low-dose IL-2 and oral RA is more effective than IL-2 alone in improving all known prognostically significant parameters in a variety of solid tumors, including an increase of lymphocytes and a decrease of VEGF.
authors.affiliation: Unità operativa di Oncologia, Ospedale Civile di Avezzano, Italy. frecchia1946@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Gaetano
authors.initials: G
authors.lastname: Saggio
authors.forename: Alisia
authors.initials: A
authors.lastname: Cesta
authors.forename: Edoardo
authors.initials: E
authors.lastname: Alesse
authors.forename: Rita
authors.initials: R
authors.lastname: Gallo
authors.forename: Stefano
authors.initials: S
authors.lastname: Necozione
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D018572:Disease-Free Survival; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D042461:Vascular Endothelial Growth Factor A; D015474:Isotretinoin