Preliminary results from a randomized phase III trial of adjuvant interleukin-2, interferon alpha and 5-fluorouracil in patients with a high risk of relapse after nephrectomy for renal cell carcinoma (RCC)
Aitchison, M. Bray, C. Van Poppel, Hendrik Sylvester, R. Graham, J. Innes, C. McMahon, L. Vasey, P.A. #
Grune & Stratton
Journal of Clinical Oncology vol:26 issue:15 pages:259-259
Background: Despite an apparently curative resection, 30% of patients with RCC will develop metastases. Histological risk factors can predict those at highest risk. The role of adjuvant treatment remains unclear. The aim of the present study was to determine if triple therapy improves disease free (dfs) or overall survival (os). Methods: Patients 8 weeks post nephrectomy for RCC without macroscopic residual disease with stage T3b-c,T4 or any pT and pN 1 or pN 2 or positive microscopic margins or microscopic vascular invasion, and no metastases were randomised to receive either adjuvant treatment (regimen in table below) or to observation only. Quality of life was assessed by EORTC QLQ C-30. Treatment delivery and toxicity were monitored. The trial was designed to detect an increase in 3 year dfs from 50 % in controls to 65 % on treatment (hazard ratio (HR)=0.63) with 90% power and 2-sided alpha = 0.05; this requires 308 patients and 200 events. Preliminary data release has been approved by the IDMC. Results: From1998 to 2007, 309 patients were randomised (67% male/33% female) 155 to the control arm (median age 55) and 154 to treatment (median age 57). 35% did not complete the treatment, primarily due to toxicity (92% of patients experienced > grade 2, 41%> gd 3). There were no statistically significant differences between the two arms at 6 months in any QoL parameters apart from increased fatigue on the treatment arm (p=.042). At this preliminary analysis 147 patients have relapsed with 3 year dfs of 50% with control versus 60% with treatment (overall HR 0.87, 95% confidence interval (ci) 0.63–1.20).OS at 5 years is 60% for control and 68% with treatment (HR 0.91, 95% ci 0.60 -1.38) Conclusions: The treatment is associated with significant toxicity. This preliminary analysis based on 74% of required events indicates no large benefit for the regime in terms of disease free or overall survival.