Interleukin-2 and 13-cis retinoic acid as maintenance therapy in advanced ovarian cancer

Int J Oncol. 2005 Oct;27(4):1039-46.


The primary objective was to assess whether low-dose Interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) could decrease serum vascular endothelial growth factor (VEGF) and improve the immune function of patients with advanced ovarian cancer (AOC) responsive to chemotherapy. The secondary end-point was to compare the response of these patients with that of a group of control patients, treated with standard care. Forty-four patients with AOC, responding to chemotherapy and with elevated serum levels of VEGF, were entered into the study from 04/98 to 12/02. After chemotherapy, patients received self-administered subcutaneous IL-2, 1.8x10(6) IU and oral RA, 0.5 mg/kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for 1 year and with intermittent schedules for up to 5 years. Eighty-two well-matched controls were selected from a large cohort of patients of similar disease status, treated with standard therapies. A statistically significant decrease of VEGF was observed amongst the 44 evaluable patients. Lymphocyte NK counts and CD4+/CD8+ ratio improved with respect to both baseline values and controls. The progression-free survival (PFS) and overall survival (OS) curves showed a statistically significant improvement in IL-2/RA-treated patients. These preliminary data show that, after chemotherapy for AOC, the administration of low-dose subcutaneous IL-2 and oral RA is feasible, has low toxicity, is cost-effective and improves both PFS and OS.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cell Line, Tumor
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Immunotherapy / methods
  • Interleukin-2 / metabolism*
  • Isotretinoin / metabolism*
  • Killer Cells, Natural / cytology
  • Lymphocytes / cytology
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Time Factors
  • Treatment Outcome
  • Tretinoin / pharmacology
  • Vascular Endothelial Growth Factor A / metabolism


  • Interleukin-2
  • Vascular Endothelial Growth Factor A
  • Tretinoin
  • Isotretinoin