Until now, surgery,
chemotherapy and
radiotherapy have remained the mainstay of current
cancer therapy. The major limitation of chemo- and
radiotherapy is their narrow therapeutic index between
cancer and normal cells. In the search for less toxic and more specific
therapies, various modalities of
immunotherapy have been tried. It is now increasingly recognised that patients presenting with minimal
cancer burden or micrometastatic disease will experience the greatest benefit from treatment with
monoclonal antibodies (mAbs). The first proof of efficacy of a
monoclonal antibody in
minimal residual disease has recently been published, with
mAb 17-1A in patients with
colorectal cancer stage III after complete resection of the primary tumour. After a median follow-up of 5 years, antibody
therapy reduced the overall death rate by 30% and decreased the recurrence rate by 27%. This result is similar to the benefit obtained in (radio)
chemotherapy trials, however, with notably lesser toxicity. It is clear from past experience that all currently available treatment modalities for
cancer are far from perfect. However, because the mechanism of action or target cells of different treatment modalities may be complementary in the control of tumour growth, the next logical step is to rationally design clinical trials that combine conventional chemo-, hormonal or
radiation therapy with immuno- or
biotherapy.