Is treatment with interferon-α effective in all patients with metastatic renal carcinoma?: A new approach to the investigation of interactions

The first analysis of the MRC RE01 trial in metastatic renal carcinoma identified a 28% reduction in the hazard of death for patients treated with interferon-a compared with medroxyprogesterone acetate (MPA). No subgroup was identified in which treatment with interferon-alpha was more or less effective than MPA. We used a new approach based on fractional polynomials to investigate the updated data from this trial for the possible interaction of treatment with prognostic factors. In the spirit of hypothesis generation, we considered 10 possible prognostic variables, of which white cell count (WCC) was found to influence the effectiveness of interferon treatment. In patients treated with MPA, there was no prognostic effect of WCC, whereas, in patients treated with interferon, the risk of dying increased significantly with WCC level. We defined subgroups of patients based on WCC levels and estimated a hazard ratio of 0.53 in favour of interferon in patients with WCC < 6.5 x 10(9), whereas for patients with WCC > 10 x 10(9) the risk appears to be similar between the treatment groups, or even slightly raised in the interferon group. Since our results are derived from flexible statistical models, they may be interpreted as a new hypothesis and require validation in independent data.