Currently, the prognosis for patients suffering from metastatic renal cell
carcinoma (RCC) is bleak. Despite encouraging results from studies of new
treatments, a recent review suggests that these need further assessment in large
The report notes that chemotherapeutic agents,
radiation and hormones are generally unsuccessful. RCC shows a variable natural
history characterized by late relapse after nephrectomy, prolonged stabile
metastatic disease and spontaneous regression. The authors remark that these
characteristics suggest that immune mechanisms may regulate tumour growth. As a
result, a number of therapeutic strategies now aim to modulate the host immune
response - including cytokines, adoptive immunotherapy, gene therapy and
While interferons (IFN) are widely used, only 12
per cent of metastatic RCCs show objective responses and complete remissions are
rare. High-dose intravenous interleukin-2 (IL-2) is more effective rates, but
causes considerable toxicity. Combining the two drugs produces a better outcome
than that associated with either agent alone.
The authors add that
studies adding 5-fluoro-uracil and 13-cis-retinoic acid to IFN plus IL-2 show
encouraging results. Similarly, trials of tumour-infiltrating lymphocytes,
autolymphocyte therapy with activated memory-T cells, ex vivo primed cytotoxic T
cells or dendritic cells are also showing promising results.
is also being investigated as a possible RCC treatment. For example, ex vivo
gene transfer, as a tumour cell vaccine, and intralesional in vivo gene therapy
are undergoing assessment as a way to boost tumour cell immunogenicity. A
monoclonal antibody against RCC is also being assessed as a new diagnostic test
However, despite these efforts, cure rates are low and a
standard therapy is unavailable. So if systemic therapy does not produce
palliation, clinicians need to treat tumour-related symptoms with "aggressive
supportive therapy." Assessing therapy-related quality of life will become
increasingly important, say the authors.
The researchers recommend that
as many patients as possible be enrolled in controlled studies. Despite
encouraging results with the new treatment strategies reviewed in this paper,
further assessment in large randomised trials is still needed.