COMPARISON OF EQUITOXIC RADIOIMMUNOTHERAPY AND CHEMOTHERAPY IN THE TREATMENT OF HUMAN COLONIC-CANCER XENOGRAFTS

The therapeutic efficacy of 5-fluorouracil (5-FUra; 0.6 mg/day x 5 day s) + leucovorin (LV; 1.8 mg/day x 5 days) and of I-131-labeled MN-14 a nticarcinoembryonic antigen IgG (275 muCi single dose) was evaluated i n 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 v arying 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 admi nistration was found. Therefore, it is reasonable to compare single cy cles of both treatment modalities. RAIT was statistically more effecti ve 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 r esponded well to both therapies. The lack of a statistical difference between the 2 modalities of treatment may indicate that the efficacy o f 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 efficacio us in the HT-29 and the HCT-15 tumor lines. Of the 5 xenografts that r esponded better to RAIT, 3 lines (LS174T, GW-39, and WidR) demonstrate d 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 perce nt of tumors responding to both therapies, but a greater growth inhibi tion in those RAIT-treated tumors that responded. In vitro responsiven ess to 5-FUra/LV did not directly correlate with in vivo responsivenes s (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 in hibition from RAIT also did not correlate with total tumor carcinoembr yonic antigen content (r2 = 0.003), an observation that may be due to additional variables, such as accessibility of antigen and innate radi osensitivity of the tumor. RAIT was most effective in the fastest grow ing tumor lines (LS174T, GW-39, MOSER, WidR, and LoVo). These preclini cal results suggest an advantage to radioantibody therapy over one of the most commonly used forms of chemotherapy to treat colorectal cance r. These studies also highlight the need to establish criteria that wi ll enable the selection of therapeutic modalities in patients.