Clinical and Translational Oncology

, Volume 15, Issue 9, pp 698–704 | Cite as

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

  • J. P. MarotoEmail author
  • X. G. del Muro
  • B. Mellado
  • J. L. Perez-Gracia
  • R. Andrés
  • J. Cruz
  • E. Gallardo
  • M. Domenech
  • J. Á. Arranz
  • J. A. Meana
Research Article



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.


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.


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 %).


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


Sequential treatment Immunotherapy Sorafenib Renal cell carcinoma 



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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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2013

Authors and Affiliations

  • J. P. Maroto
    • 1
    Email author
  • X. G. del Muro
    • 2
  • B. Mellado
    • 3
  • J. L. Perez-Gracia
    • 4
  • R. Andrés
    • 5
  • J. Cruz
    • 6
  • E. Gallardo
    • 7
  • M. Domenech
    • 8
  • J. Á. Arranz
    • 9
  • J. A. Meana
    • 10
  1. 1.Hospital de la Santa Creu i Sant PauBarcelonaSpain
  2. 2.Institut Català d’OncologiaBarcelonaSpain
  3. 3.Hospital Clínic i Provincial de BarcelonaBarcelonaSpain
  4. 4.Oncology DepartmentClinica Universidad de NavarraNavarraSpain
  5. 5.Hospital Universitario Lozano BlesaZaragozaSpain
  6. 6.Hospital Universitario de CanariasSan Cristóbal de La LagunaSpain
  7. 7.Corporació Sanitària Parc Taulí de SabadellSabadellSpain
  8. 8.ALTHAIA Xarxa Assistencial de ManresaBarcelonaSpain
  9. 9.Hospital Gregorio MarañonMadridSpain
  10. 10.Hospital General Universitario de AlicanteAlicanteSpain

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