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Phase II trial of sequential subcutaneous interleukin-2 plus interferon alpha followed by sorafenib in renal cell carcinoma (RCC)

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Abstract

Purpose

Immunotherapy (IL-2 and INF-α) was the treatment of choice for advanced renal cell carcinoma (RCC) until antiangiogenic therapy with tyrosin kinase inhibitors was developed in the early 2000s. This clinical trial explored the efficacy and toxicity of sequential treatment of IL-2 plus INF-α followed by sorafenib.

Methods

Eligibility criteria included measurable, non-resectable, histologically confirmed predominantly clear cell RCC, no prior systemic treatment, and ECOG PS 0–2. The treatment regimen was a 6-week cycle of subcutaneous IL-2 at 9 × 106 IU on days 1–6 of weeks 1, 2, 4 and 5 plus s.c. INF-α at 6 × 106 IU on days 1, 3 and 5 of weeks 1–6. Responders received 6 additional weeks of this regimen. All patients received oral sorafenib (400 mg bid) after immunotherapy until disease progression. The primary endpoint was progression-free survival.

Results

Forty-one patients were enrolled, median age 57 years. ECOG was 0/1 in 17/20 patients, 35 patients had prior nephrectomy and 18 patients pure clear cell cancer. Median PFS was 7.4 months (95 % CI 6.5–13.1) and OS was 16.6 months (95 % CI not reached). In 36 patients evaluable for response, ORR was 44.4 % and control rate was 94.4 %. Most adverse events (AEs) were Grade 1 or 2 toxicities (84.7 %). During immunotherapy the most common AEs were pyrexia (82.9 %), asthenia (56.1 %) and anorexia (46.3 %), whereas during sorafenib were diarrhoea (48.8 %) and hand–foot syndrome (46.3 %).

Conclusions

A sequential regimen of IL-2 and INF-α followed by sorafenib showed effectiveness and manageable toxicity in patients with advanced RCC.

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Acknowledgments

We are grateful to the patients who participated in this trial. Funding for this study was provided by Bayer Hispania S.L.

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Authors and Affiliations

  1. Hospital de la Santa Creu i Sant Pau, Mas Casanovas 90, 08025, Barcelona, Spain

    J. P. Maroto

  2. Institut Català d’Oncologia, Barcelona, Spain

    X. G. del Muro

  3. Hospital Clínic i Provincial de Barcelona, Barcelona, Spain

    B. Mellado

  4. Oncology Department, Clinica Universidad de Navarra, Navarra, Spain

    J. L. Perez-Gracia

  5. Hospital Universitario Lozano Blesa, Zaragoza, Spain

    R. Andrés

  6. Hospital Universitario de Canarias, San Cristóbal de La Laguna, Spain

    J. Cruz

  7. Corporació Sanitària Parc Taulí de Sabadell, Sabadell, Spain

    E. Gallardo

  8. ALTHAIA Xarxa Assistencial de Manresa, Barcelona, Spain

    M. Domenech

  9. Hospital Gregorio Marañon, Madrid, Spain

    J. Á. Arranz

  10. Hospital General Universitario de Alicante, Alicante, Spain

    J. A. Meana

Authors
  1. J. P. Maroto
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  2. X. G. del Muro
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  3. B. Mellado
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  4. J. L. Perez-Gracia
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  6. J. Cruz
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  7. E. Gallardo
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  8. M. Domenech
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Corresponding author

Correspondence to J. P. Maroto.

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Maroto, J.P., del Muro, X.G., Mellado, B. et al. Phase II trial of sequential subcutaneous interleukin-2 plus interferon alpha followed by sorafenib in renal cell carcinoma (RCC). Clin Transl Oncol 15, 698–704 (2013). https://doi.org/10.1007/s12094-012-0991-z

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  • DOI: https://doi.org/10.1007/s12094-012-0991-z

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