- J. Stebbing and M. Gore (The Department of Medicine, The Royal Marsden NHS Trust, London, UK)
The Current Status of Interferon-a Treatment in Advanced Renal Cancer
BJU Intl. May 2001 Vol. 87 (7) Pg. 599-601
Introduction : RCC is the 10th commonest malignancy and causes an estimated 95 000 deaths per year worldwide.
Localized RCC can be cured by surgery. Despite apparently localized disease at presentation, 20-30% of patients relapse after radical nephrectomy, usually with distant metastases. Metastatic RCC is often highly variable in its clinical course, including spontaneous regressions.
The most promising therapy for metastatic RCC is immunobiological therapy.
The exact mechanism of action is debatable but immuno-therapy may act by:
1) Stimulating phagocytosis by macrophages.
2) Up-regulating MHC class I molecules.
3) Having direct cytotoxic effect on tumor cells.
Early randomized trials suggested that biological therapy with interferon-a produced an objective tumour response rate of approximately 15% in selected patients that translated into a survival benefit.
Randomized Studies : There are 5 randomized trials comparing treatments including interferon-a or otherwise for metastatic disease.
3 of these showed a survival benefit with the use of interferon in a total of 573 patients and other 2 studies involved relatively few patients (n = 136 in total).
There was a 28% reduction in the risk of death in the interferon-a group and the objective response rate at 12 weeks in this group was 14% compared with 2% in patients receiving medroxyprogesterone acetate (MPA) 300 mg/day orally.
Side effects and toxicity : 2/3rds of patients on interferon-a reported mild to moderate symptoms of ‘influenza’, fever, nausea, depression, loss of appetite and fatigue; toxicity at the injection site is rare.
At the Royal Marsden NHS Trust, a phase II trial combining interferon-a with thalidomide is underway.
Thalidomide has been previously shown to have anti-angiogenic activity in several tumour models, and is associated with disease stabilization and objective responses in this metastatic RCC.
Summary / Conclusion : The results indicate that interferon-a is superior to controls and the pooled hazard ratio for survival of 0.78 indicates that the treatment effect persisted for 24 months.
The independent reviewers have suggested that interferon-a 10 MU subcutaneously 3 times per week is the standard treatment and should represent the control arm of future studies.