Adjuvant 5-flurouracil, alpha-interferon and interleukin-2 versus observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma: results of a phase III randomised European Organisation for Research and Treatment of Cancer (Genito-Urinary Cancers Group)/National Cancer Research Institute trial.
BACKGROUND
The purpose of this trial was to compare adjuvant 5-flurouracil, alpha-interferon and interleukin-2 to observation in patients at high risk of recurrence after nephrectomy for renal cell carcinoma (RCC) in terms of disease free survival, overall survival and quality of life (QoL).


METHODS
Patients 8weeks post nephrectomy for RCC, without macroscopic residual disease, with stage T3b-c,T4 or any pT and pN1 or pN2 or positive microscopic margins or microscopic vascular invasion, and no metastases were randomised to receive adjuvant treatment or observation. QoL was assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQC-30). Treatment delivery and toxicity were monitored. The trial was designed to detect an increase in 3year disease free survival (DFS) from 50% on observation to 65% on treatment (hazard ratio (HR)=0.63) with 90% power and two-sided alpha=0.05.


RESULTS
From 1998 to 2007, 309 patients were randomised (155 to observation; 154 to treatment). 35% did not complete the treatment, primarily due to toxicity (92% of patients experienced ⩾grade 2, 41% ⩾grade 3). Statistically significant differences between the arms in QoL parameters at 2months disappeared by 6months although there was suggestion of a persistent deficit in fatigue and physical function. Median follow-up was 7years (maximum 12.1years). 182 patients relapsed or died. DFS at 3years was 50% with observation and 61% with treatment (HR 0.84, 95% confidence interval (CI) 0.63-1.12, p=0.233). 124 patients died. Overall survival (OS) at 5years was 63% with observation and 70% with treatment (HR 0.87, 95% CI 0.61-1.23, p=0.428).


CONCLUSIONS
The treatment is associated with significant toxicity. There is no statistically significant benefit for the regimen in terms of disease free or overall survival.
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom. Electronic address: michael.aitchison@nhs.net.
M
M
Aitchison
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
C A
CA
Bray
Urology Section, K.U. Leuven, Belgium.
H
H
Van Poppel
EORTC Headquarters, Brussels, Belgium.
R
R
Sylvester
Musgrove Park Hospital, Taunton, United Kingdom.
J
J
Graham
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
C
C
Innes
The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
L
L
McMahon
School of Medicine, University of Queensland, Brisbane, Australia.
P A
PA
Vasey
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009392:Nephrectomy; D011788:Quality of Life; D012008:Recurrence; D012307:Risk Factors; D011795:Surveys and Questionnaires
D016898:Interferon-alpha; D007376:Interleukin-2; D005472:Fluorouracil
Adjuvant chemotherapy; Nephrectomy; Renal cell carcinoma