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Combined Radioimmunotherapy and Radiotherapy of Human Colon Carcinoma Grafted in Nude Mice¹

Division of Nuclear Medicine [F. B., A. B. D., C-A. V., L-Q. S., B. D.] and Department of Radio-Oncology [F. B., R-O. M., P. C.], Centre Hospitalier Universitaire Vaudois, CH 1011 Lausanne, Switzerland; "Institut de Radiophysique Appliquée" [S. R.], CH 1015 Lausanne, Switzerland; Cancer Research Campaign Gray Laboratory, Mount Vernon Hospital, Northwood HA62 YR, United Kingdom [A. R., J. D.]; and Institute of Biochemistry, University of Lausanne, CH 1006 Epalinges, Switzerland [A. P., J-P. M.]

The effect of combined radioimmunotherapy (RIT) and fractionated external beam radiotherapy (RT) was assessed in two human colon cancer xenografts, Co112 and LS174T in nude mice. These tumors were selected for being resistant to RIT alone, as is usually the case in the clinical situation. Tumor-bearing mice were treated with a combination of five X-ray fractions over 5 days followed by RIT with two doses of 1.5 mCi ¹³¹I-labeled anticarcinoembryonic antigen monoclonal antibody F(ab')₂. In Co112 and LS174T, RIT alone achieved a regrowth delay similar to that of fractionated RT with total doses of 28 and 26 Gy, respectively. In both tumor types, an additive therapeutic effect, measured as increased regrowth delay or local control, was observed when combining RT of different dose levels with RIT. Normal tissue responses were assessed by monitoring acute peak skin reactions and blood cell count. Bone marrow depression for the combination treatment was similar to that of RIT alone; relative to skin, at equitoxic levels, no mice bearing Co112 tumors were locally controlled with a 32 Gy RT dose alone, while this RT combined with RIT gave a local control of 100%. These studies show a therapeutic benefit when external beam RT is combined with RIT.

¹ This work was supported by the Swiss Foundation for Scientific Research Grant 31-31238-91, the foundation "Swiss Research Against Cancer" (Akt 312), and the Swiss Robert Wenner Cancer Research Award 1991.

² To whom requests for reprints should be addressed.

Received 7/ 5/94. Accepted 10/31/94.

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