Phase I trial of sunitinib malate plus interferon-alpha for patients with metastatic renal cell carcinoma

Clin Genitourin Cancer. 2009 Jan;7(1):28-33. doi: 10.3816/CGC.2009.n.005.


Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor that has demonstrated superior efficacy over interferon (IFN)-alpha in a phase III trial in first-line, metastatic renal cell carcinoma (RCC). Herein, we report the results of a phase I dose-finding study of sunitinib in combination with IFN-alpha as first-line treatment in patients with metastatic RCC.

Patients and methods: Treatment-naive patients with clear-cell metastatic RCC received sunitinib at a starting dose of 50 mg or 37.5 mg orally once daily in 6-week cycles (schedule 4/2) plus IFN-alpha at a starting dose of 3 MU subcutaneously 3 times a week, with weekly intrapatient dose escalation to a maximum of 9 MU as tolerated. Patients who did not tolerate either drug received lower doses of either or had dose interruptions.

Results: Twenty-five patients were enrolled; their median age was 64 years (range, 45-77 years). All patients experienced grade 3/4 treatment-emergent adverse events; the most common were neutropenia, fatigue, and thrombocytopenia. After a median of 4 cycles (range, 1-9 cycles), 3 patients (12%) had a partial response, and 20 (80%) had stable disease.

Conclusion: Although reduced starting doses were tolerated (37.5 mg for sunitinib and 3 MU for IFN-alpha), even these lower doses might not be well tolerated for long-term treatment of patients with metastatic RCC. Based on historical data, sunitinib on schedule 4/2 appears to be more effective as single-agent therapy. Further study of sunitinib plus IFN-alpha on this schedule is not being pursued in RCC.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Fatigue / chemically induced*
  • Female
  • Humans
  • Indoles / administration & dosage
  • Interferon-alpha / administration & dosage
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neutropenia / chemically induced*
  • Pyrroles / administration & dosage
  • Sunitinib
  • Thrombocytopenia / chemically induced*
  • Treatment Outcome


  • Indoles
  • Interferon-alpha
  • Pyrroles
  • Sunitinib