Cancer Immunology, Immunotherapy

, Volume 56, Issue 5, pp 699–708 | Cite as

Phase II study of interleukin-2 and 13-cis-retinoic acid as maintenance therapy in metastatic colorectal cancer

  • Francesco Recchia
  • Gaetano Saggio
  • Alisia Cesta
  • Giampiero Candeloro
  • Anna Di Blasio
  • Giovanna Amiconi
  • Marco Lombardo
  • Antonio Nuzzo
  • Angelo Lalli
  • Edoardo Alesse
  • Stefano Necozione
  • Silvio Rea
Original Article



We have previously shown that low-dose interleukin-2 (IL-2) and 13-cis-retinoic acid (13-cis-RA) improved lymphocyte and natural killer (NK) cell count of patients with advanced tumors showing a clinical benefit from chemotherapy. The primary endpoint of this study was to ask whether IL-2 and 13-cis-RA improved (-0%) lymphocyte and NK cell count in patients with metastatic colorectal cancer (MCRC) that had a clinical benefit from induction chemotherapy. Secondary endpoint was the evaluation of toxicity, progression-free survival (PFS), and overall survival (OS).

Patients and methods

Forty patients with MCRC, showing a clinical benefit from chemotherapy, were treated with subcutaneous low-dose IL-2 (1.8 × 106 IU) and oral 13-cis-RA (0.5 mg/kg) in order to maintain responses and improve survival through the increase of lymphocyte and NK cells. The biological parameters and the clinical outcome of these patients were compared with those of a control group of patients (80) with a similar disease status, including clinical benefit from chemotherapy.


The most common adverse events were mild cutaneous skin rash and fever. After 4 months and 2 years of biotherapy, a statistically significant improvement was observed in lymphocyte and number of NK cells with respect to baseline values and to controls. After a median follow-up of 36 months, median PFS was 27.8 months, while median OS was 52.9 months.


These data show that maintenance immunotherapy with low-dose IL-2 and oral 13-cis-RA in patients with MCRC showing a clinical benefit from chemotherapy is feasible, has a low toxicity profile, improves lymphocyte and NK cell count. An improvement in the expected PFS and OS was also observed. A randomized trial is warranted.


Maintenance therapy Metastatic colorectal cancer Interleukin-2 13-cis-retinoic acid Lymphocyte Natural killer cells 


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Francesco Recchia
    • 1
    • 2
    • 9
  • Gaetano Saggio
    • 1
  • Alisia Cesta
    • 1
  • Giampiero Candeloro
    • 1
  • Anna Di Blasio
    • 1
  • Giovanna Amiconi
    • 1
  • Marco Lombardo
    • 3
  • Antonio Nuzzo
    • 4
  • Angelo Lalli
    • 5
  • Edoardo Alesse
    • 6
  • Stefano Necozione
    • 7
  • Silvio Rea
    • 2
    • 8
  1. 1.Unità operativa di OncologiaOspedale Civile di AvezzanoAvezzanoItaly
  2. 2.Fondazione “Carlo Ferri”RomaItaly
  3. 3.Unità operativa di OncologiaOspedale Civile di PescaraPescaraItaly
  4. 4.Unità operativa di OncologiaOspedale Civile di LancianoLancianoItaly
  5. 5.Unità operativa di OncologiaOspedale Civile di GiulianovaGiulianovaItaly
  6. 6.Patologia GeneraleUniversità degli Studi de L’AquilaL’AquilaItaly
  7. 7.Epidemiologia ClinicaUniversità degli Studi de L’AquilaL’AquilaItaly
  8. 8.Chirurgia OncologicaUniversità degli Studi de L’AquilaL’AquilaItaly
  9. 9.Luco dei Marsi (AQ)Italy

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