Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators

Lancet. 1999 Jan 2;353(9146):14-7.


Background: Metastatic renal carcinoma has a 2-year survival of around 20% and is largely resistant to chemotherapy. The use of interferons in the treatment of metastatic renal carcinoma remains controversial. Although non-randomised studies suggest that biological therapy with interferons produces a small number of tumour responses, most clinicians judge such treatment to be ineffective. We have investigated the effect of treatment with interferon-alpha on survival in patients with metastatic renal carcinoma.

Methods: In a multicentre, randomised trial, patients with metastatic renal carcinoma were randomly assigned subcutaneous interferon-alpha (three doses--5 MU, 5 MU, 10 MU--for the first week, then 10 MU three times per week for a further 11 weeks; n=174) or oral medroxyprogesterone acetate (MPA; 300 mg once daily for 12 weeks; n=176). The primary endpoint was overall survival. Analysis was by intention to treat. The trial used a triangular sequential design for early termination as soon as results were conclusive. The trial was stopped in November, 1997, when data were available for 335 patients (167 interferon-alpha, 168 MPA).

Findings: A total of 111 patients have died in the interferon-alpha group, and 125 patients have died in the MPA group. There was a 28% reduction in the risk of death in the interferon-alpha group (hazard ratio 0.72 [95% CI 0.55-0.94], p=0.017). Interferon-alpha gave an improvement in 1-year survival of 12% (MPA 31% survival, interferon-alpha 43%), and an improvement in median survival of 2.5 months (MPA 6 months, interferon-alpha 8.5 months).

Interpretation: The benefit of treatment with interferon-alpha should be weighed against the drug's toxic effects. Combination regimens of biological therapy and chemotherapy should now be compared with interferon-alpha monotherapy in randomised controlled trials.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Female
  • Humans
  • Interferon-alpha / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Medroxyprogesterone Acetate / therapeutic use
  • Middle Aged
  • Neoplasm Metastasis
  • Nephrectomy
  • Registries
  • Survival Analysis
  • United Kingdom


  • Antineoplastic Agents
  • Antineoplastic Agents, Hormonal
  • Interferon-alpha
  • Medroxyprogesterone Acetate