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Comparison of Equitoxic Radioimmunotherapy and Chemotherapy in the Treatment of Human Colonic Cancer Xenografts¹

Garden State Cancer Center at the Center for Molecular Medicine and Immunology, Newark, New Jersey 07103 [R. D. B., R. M., A. M. N., R. K., D. M. G.], and Memorial Sloan Kettering Cancer Center, Division of Biostatistics, New York, New York 10029 [G. W.]

² To whom requests for reprints should be addressed, at Center for Molecular Medicine and Immunology, 1 Bruce Street, Newark, NJ 07103.

The therapeutic efficacy of 5-fluorouracil (5-FUra; 0.6 mg/day x 5 days) + leucovorin (LV; 1.8 mg/day x 5 days) and of ¹³¹I-labeled MN-14 anticarcinoembryonic antigen IgG (275 µCi single dose) was evaluated in size-matched (0.3–0.7 cm³) s.c. LoVo, HT-29, DLD-1, HCT-15, LS174T, and MOSER, GW-39, and WidR human colonic tumors. These lines express varying amounts of carcinoembryonic antigen and exhibit varying degrees of in vitro responsiveness to 5-FUra. Unlike radioimmunotherapy (RAIT), multiple cycles of chemotherapy were feasible over a 3-week period. However, no therapeutic advantage to a second cycle of 5-FUra/LV administration was found. Therefore, it is reasonable to compare single cycles of both treatment modalities. RAIT was statistically more effective in 5 of 8 tumor lines (LoVo, LS174T, MOSER, WidR, and GW-39). In 1 other line (DLD-1), RAIT was marginally more efficacious, but tumors responded well to both therapies. The lack of a statistical difference between the 2 modalities of treatment may indicate that the efficacy of the 2 treatments is equivalent, or the relatively large variability within the treatment groups may have prevented significance given the number of animals evaluated. RAIT and 5-FUra/LV were equally efficacious in the HT-29 and the HCT-15 tumor lines. Of the 5 xenografts that responded better to RAIT, 3 lines (LS174T, GW-39, and WidR) demonstrated a greater percentage of tumors responding over a 5- to 6-week period. The other 3 lines (LoVo, MOSER, and DLD-1) exhibited a similar percent of tumors responding to both therapies, but a greater growth inhibition in those RAIT-treated tumors that responded. In vitro responsiveness to 5-FUra/LV did not directly correlate with in vivo responsiveness (r² = –0. 664), since LS174T and LoVo tumors, with rapid growth rates (0.05–0.36 cm³/day), were not highly responsive to therapy. Growth inhibition from RAIT also did not correlate with total tumor carcinoembryonic antigen content (r² = 0.003), an observation that may be due to additional variables, such as accessibility of antigen and innate radiosensitivity of the tumor. RAIT was most effective in the fastest growing tumor lines (LS174T, GW-39, MOSER, WidR, and LoVo). These preclinical results suggest an advantage to radioantibody therapy over one of the most commonly used forms of chemotherapy to treat colorectal cancer. These studies also highlight the need to establish criteria that will enable the selection of therapeutic modalities in patients.

¹ Supported in part by United States Department of Health and Human Services Grants CA37895 and CA39841 from the NIH.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 3/ 4/93. Accepted 10/28/93.

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