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

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Abstract

Purpose

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.

Results

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.

Conclusion

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.

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Authors and Affiliations

  1. Unità operativa di Oncologia, Ospedale Civile di Avezzano, Avezzano, Italy

    Francesco Recchia, Gaetano Saggio, Alisia Cesta, Giampiero Candeloro, Anna Di Blasio & Giovanna Amiconi

  2. Fondazione “Carlo Ferri”, Monterotondo, Roma, Italy

    Francesco Recchia & Silvio Rea

  3. Unità operativa di Oncologia, Ospedale Civile di Pescara, Pescara, Italy

    Marco Lombardo

  4. Unità operativa di Oncologia, Ospedale Civile di Lanciano, Lanciano, Italy

    Antonio Nuzzo

  5. Unità operativa di Oncologia, Ospedale Civile di Giulianova, Giulianova, Italy

    Angelo Lalli

  6. Patologia Generale, Università degli Studi de L’Aquila, L’Aquila, Italy

    Edoardo Alesse

  7. Epidemiologia Clinica, Università degli Studi de L’Aquila, L’Aquila, Italy

    Stefano Necozione

  8. Chirurgia Oncologica, Università degli Studi de L’Aquila, L’Aquila, Italy

    Silvio Rea

  9. Via Rossetti 1, 67056, Luco dei Marsi (AQ), Italy

    Francesco Recchia

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  1. Francesco Recchia
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  2. Gaetano Saggio
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  9. Angelo Lalli
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  11. Stefano Necozione
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Correspondence to Francesco Recchia.

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Recchia, F., Saggio, G., Cesta, A. et al. Phase II study of interleukin-2 and 13-cis-retinoic acid as maintenance therapy in metastatic colorectal cancer. Cancer Immunol Immunother 56, 699–708 (2007). https://doi.org/10.1007/s00262-006-0224-9

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  • DOI: https://doi.org/10.1007/s00262-006-0224-9

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