Chemopreventive effects of Iressa against methylnitrosourea (MNU) induced mammary cancers and 4-hydroxybutyl(butyl)-nitrosamine (OH-BBN) induced urinary bladder cancers

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The efficacy of the Epidermal Growth Factor receptor (EGFr) inhibitor Iressa as a preventive and therapeutic agent against MNU induced mammary cancers and OH-BBN induced urinary bladder cancers was determined. In the mammary cancer model, female Sprague-Dawley rats were given a single dose of MNU (75 mg/kg BW), IV, at 50 days of age. Iressa treatment was initiated five days later and continued until the end of the study (126 days after MNU). Iressa was administered by gavage 6x/week (vehicle was ethanol: polyethylene glycol 400 (10:90, v/v). At termination of the study, the average number of mammary cancers/rat was as follows: controls, 4.0; Iressa (10 mg/kg BW/day), 3.1; Iressa (3 mg/kg BW/day), 2.1; and Iressa (1.0 mg/kg BW/day), 0.5. In the therapy experiment when a MNU-treated rat developed a small (200-300 mm²) mammary cancer, the animal was treated with either Iressa (10 mg/kg BW/day) or the vehicle for 5 weeks. Mammary tumors in 7 of 10 Iressa-treated rats underwent complete regression, while 9 of 10 vehicle-treated rats had progressive (albeit variable) growth of their tumors. Thus, the Iressa dose that was effective as a preventive agent was also effective as a therapeutic agent. In the OH-BBN induced urinary bladder cancer model, female Fischer-344 rats were administered OH-BBN by gavage 2x/week for eight weeks. One week following the last dose of OH-BBN, the animals were given Iressa at either 5 or 10 mg/kg BW/day. Both doses of Iressa inhibited the formation of large palpable bladder tumors by greater than 85%. Therefore, this EGFr inhibitor was highly effective in preventing cancers in animal models of two different organs.