Treatment and survival study in the C57BL/6J-APC(Min)/+(Min) mouse with R-flurbiprofen.

Area of Science:

• Pharmacology and Oncology
• Preclinical Cancer Research
• Drug Efficacy Studies

Background:

• Familial adenomatous polyposis (FAP) is a genetic disorder predisposing individuals to colorectal cancer.
• Previous studies identified 10 mg/kg/day of R-flurbiprofen as optimal for adenoma reduction in the Min mouse model.
• The efficacy of different dosing schedules and comparison with sulindac sulfone required further investigation.

Purpose of the Study:

• To evaluate the impact of daily (qd) versus every-other-day (q.o.d.) dosing of R-flurbiprofen (10 mg/kg) on survival and tumor reduction in Min mice.
• To compare the efficacy of R-flurbiprofen with sulindac sulfone in the FAP mouse model.
• To explore the relationship between drug administration schedule and therapeutic outcomes.

Main Methods:

• Utilized the C57BL/6J-APC(Min)/+ (Min) mouse model for familial adenomatous polyposis.
• Administered R-flurbiprofen at 10 mg/kg/day (qd) and 10 mg/kg every-other-day (q.o.d.), and sulindac sulfone at 50 mg/kg/day.
• Monitored survival, tumor number, tumor area, body weight gain, and hematocrit levels.

Main Results:

• R-flurbiprofen (10 mg/kg) significantly increased survival compared to vehicle control (p=0.0004).
• Both qd and q.o.d. R-flurbiprofen regimens reduced tumor number significantly (p<0.01).
• The q.o.d. schedule showed improved body weight gain (p<0.01), hematocrit (p<0.05), and average tumor area (p<0.05) compared to qd dosing.
• Sulindac sulfone (50 mg/kg/day) demonstrated no significant biological benefit.

Conclusions:

• R-flurbiprofen administration dramatically prolongs survival in the FAP mouse model.
• Tumor reduction may necessitate achieving a threshold drug concentration rather than continuous sustainment.
• The q.o.d. dosing schedule of R-flurbiprofen offers comparable efficacy to daily dosing with improved physiological parameters.