Abstract P1-08-03: Alternative Dosing Regimens with Tarceva in a Mammary Cancer Model: Effects on Efficacy and Potential Effects on Toxicity

The EGFR inhibitors (e.g., Tarceva) have been effective in preventing cancer in multiple animal models, including ER positive breast, head and neck, and urinary bladder cancers. Although Tarceva is less toxic than most classical cytotoxic therapies, the development of a skin rash in greater than 35% of patients is a significant impediment to its use in a preventive setting. We, therefore, tested whether alternative dosing regimens would still achieve preventive efficacy. Female Sprague-Dawley rats were administered a single IV dose of methylnitrosourea at 50 days of age. Beginning 5 days later, rats were administered Tarceva (6 mg/kg BW) by gavage. In the first study, three different protocols were employed: (1) dosing with Tarceva daily (7X/week), (2) dosing with Tarceva for one day followed by one day of vehicle treatment, and (3) two days of dosing with Tarceva followed by two days of dosing with vehicle treatment. These treatment regimens resulted in 94, 58, and 77% decreases, respectively, in cancer multiplicity when compared to rats receiving vehicle alone. In a second ongoing study, we are evaluating the following alternative dosing schedules. MNU treated rats are receiving either: (1) daily dosing with 6 mg/kg BW (total of 42 mg/week); (2) dosing 6 mg/kg BW, 2 days on-2 days off (total of 21 mg/week): (3) weekly dosing with a single dose of 42 mg; and (4) daily dosing with the vehicle. The various Tarceva treatment regimens have currently reduced palpable mammary tumor multiplicity by 82, 66, and 71%, respectively. These data imply that by significantly altering the dosing of Tarceva, including a dose of once per week, most of the preventive efficacy is retained. Pharmacokinetic studies from these protocols showed a t½ of Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-03.