For renal cell carcinoma patients at high risk of relapse following nephrectomy, adjuvant therapy with the combination of interleukin-2 (Proleukin), interferon alfa, and fluorouracil (5-FU) provides no survival benefit over observation alone, according to a phase III trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC). Michael Aitchison, MD, of the Beatson Oncology Centre in Glasgow, presented the final results of the trial at the 2011 ASCO Annual Meeting.1
Previous studies demonstrated high response rates with the combination of interleukin-2, interferon alfa, and 5-FU as first-line therapy in patients with metastatic renal cell carcinoma. Known as the Atzpodien regimen (after Dr. Jens Atzpodien, who developed it), the combination was considered the optimal adjuvant therapy in 1995, when the present trial was initiated. This EORTC/NCRI study funded by CR-UK was designed to determine if adjuvant therapy with the Atzpodien regimen improves survival compared with observation alone in patients who are at high risk of relapse following nephrectomy.
Patients were eligible for this randomized phase III trial if they were 8 weeks postnephrectomy with no macroscopic residual disease, had stage T3b-c, T4, or any pT and pN1 or pN2 or positive microscopic margins or microscopic vascular invasion, and had no metastases. The trial was designed to detect an increase in 3-year disease-free survival from 50% in the control arm to 65% with treatment (HR = 0.63), with 90% power and 2-sided alpha of 0.05. Quality of life was assessed using the EORTC QLQ C-30 instrument.
No Significant Differences
A total of 309 patients were enrolled in the trial (68% male), including 155 on the control arm (median age, 55 years) and 154 on the treatment arm (median age, 57 years). However, 35% of patients who received the combination regimen were unable to complete therapy, largely due to treatment-related toxicity (at least grade 2 in 92% of patients, and at least grade 3 in 41%). At 6 months, no statistically significant differences were observed in any quality-of-life parameters between the two treatment arms.
With a median follow-up of 5.9 years (maximum 12.1 years), the investigators found no statistically significant survival benefit for the treatment regimen arm compared with the control arm. The 3-year disease-free survival was 61% on the treatment arm and 50% on the control arm (overall HR = 0.84; 95% CI = 0.63–1.12). Overall survival at 5 years was also similar (70% vs 63%; HR = 0.86; 95% CI = 0.60–1.22). Post hoc exploratory analysis suggested a possible difference in survival between pT1 and pT2 patients, which needs to be confirmed in additional trials. ■
Disclosure: Dr. Aitchison is a consultant for and has received honoraria from Novartis and Pfizer. Dr. Rosenberg is an employee of UBC Scientific Solutions and has previously provided medical writing support, which was funded by Pfizer.
1. Aitchison M, Bray CA, Van Poppel H, et al: Final results from an EORTC (GU Group)/NCRI 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). 2011 ASCO Annual Meeting. Abstract 4505. Presented June 6, 2011.
Commenting on the renal cell carcinoma study presented in abstract 4505 at the 2011 ASCO Annual Meeting, Walter M. Stadler, MD, of The University of Chicago, said, “The EORTC and investigators should be congratulated for conducting and completing this extremely difficult trial.” Unfortunately, he...