Interferon-α-2a with or without 13-cis retinoic acid in patients with progressive, measurable metastatic renal cell carcinoma : Results of a randomized Phase II study (European Organization for Research and Treatment of Cancer Study 30951)
✍ Scribed by Sophie D. Fosså; Gerald H. J. Mickisch; Pieter H. M. De Mulder; Simon Horenblas; Allan T. van Oosterom; Hein van Poppel; Martin Fey; Jelle J. Croles; Linda de Prijck; Martine Van Glabbeke
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 130 KB
- Volume
- 101
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
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.