Interferon-alpha-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma

Cancer. 2004 Aug 1;101(3):533-40. doi: 10.1002/cncr.20307.


Background: In patients with metastatic renal cell carcinoma (MRCC), interferon-alpha (IFN) monotherapy leads to response rates of 5-15%, dependent on the selection of patients. In 1995, preclinical and clinical data indicated an improvement of these results if IFN was combined with 13-cis retinoic acid (CRA).

Methods: In a randomized Phase II study, patients with measurable MRCC received either subcutaneous IFN (9 MU daily; Arm A) or the same daily subcutaneous dose of IFN plus oral CRA (1 mg/kg; Arm B). A central expert panel reviewed the X-ray documentation of objective responses.

Results: In the 50 eligible patients from Arm A, the objective, expert-reviewed response rate was 6% (95% confidence interval [95% CI], 1.3-16.6%; 2 complete responses [CRs] and 1 partial response [PR]). A 19% response rate (95% CI, 9.4-32.0%) was stated for 53 eligible patients from Arm B (2 CRs and 8 PRs). Only one of the four CRs claimed by the clinical investigator was confirmed by the central review committee. Conversely, the expert committee deemed that 3 of 12 investigator-stated PRs were CRs. Constitutional toxicity (flu-like symptoms) and/or side effects from skin, mucosa, or eyes led to discontinuation of treatment in 22% of nonprogressing patients, more often in Arm B than in Arm A.

Conclusions: The results from this randomized Phase II study support expansion of the trial into a Phase III study to evaluate the effect of IFN-CRA combination therapy on the survival of patients who undergo nephrectomy prior to IFN-based immunotherapy. The considerable interobserver variability of response evaluation (individual investigator vs. expert panel) indicates the necessity of a central review of claimed responses in future Phase II studies involving patients with MRCC.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / secondary*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Europe
  • Female
  • Humans
  • Injections, Subcutaneous
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Isotretinoin / administration & dosage*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging
  • Probability
  • Prognosis
  • Recombinant Proteins
  • Reference Values
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome


  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Isotretinoin