Divisions of Nuclear Medicine, Oncosurgery, and Radiooncology, University Hospital of Geneva, 1211 Geneva 14, Swizerland
Service of Nuclear Medicine, University Hospital of Lausanne, 1011 Lausanne, Switzerland
Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland
The expected therapeutic gain of a combined radioimmunotherapy
(RIT) with conventional radiotherapy (RT) would be a synergy
of tumor irradiation, provided that toxic, dose-limiting side
effects concern different organs. We have shown in a model of
subcutaneous human colon cancer transplants in nude mice that
RIT with
131I-labeled anti-CEA antibody fragments combined with
fractionated RT give an additive therapeutic effect without
increase of side effects. A second study of different timing
schedules of RIT and RT has shown that close association of
both therapies without delay is more efficient than a therapy
with a treatment-free interval of two weeks. In a new model
of human colon cancer liver metastases in nude mice, early treatment
with RIT and with RT has been curative, whereas therapies initiated
later were less efficient, suggesting that the combined therapy
is likely to be more efficient in an adjuvant situation after
surgery. At the clinical level, six patients with limited liver
metastatic disease from colorectal cancer were treated with
RIT using 200 mCi
131I-labeled anti-CEA MAb F(ab')
2 fragments
combined with fractionated external beam RT of 20 Gy to the
entire liver. As expected, spontaneously reversible bone marrow
toxicity grade 3 to 4 and reversible liver toxicity grade 1
to 3 have been observed. By computerized tomography, three patients
showed stable disease and one patient partial remission, whereas
two patients had progressive disease. In conclusion, animal
experiments have shown a clear advantage of combined RT and
RIT, and the clinical study shows the feasibility of such a
therapy in patients with colorectal cancer liver metastases.
