Encapsulated rapamycin a promising chemopreventive agent in familial adenomatous polyposis

In patients with familial adenomatous polyposis (FAP), treatment with encapsulated rapamycin is safe and appears to lower polyp burden, according to a phase II study. 

The study included 30 patients with FAP. These patients were randomly allocated to one of the three dosing regimens of encapsulated rapamycin 0.5 mg: every other day (cohort 1), daily every other week (cohort 2), or daily (cohort 3).

Safety, tolerability, and percentage change from baseline in colorectal polyp burden at 6 months were assessed as the primary endpoints. Secondary endpoints included percentage change from baseline in total and duodenal polyp burden, as well as change in International Society for Gastrointestinal Hereditary Tumors stage and Spigelman score at 6 and 12 months.

Twenty-nine patients (97 percent) completed the 12-month study with predictable bioavailability. Low-grade adverse events occurred frequently, with the highest rate observed with daily dosing in cohort 3. Toxicities resulted in treatment discontinuation in two patients.

At 6 months, patients who received encapsulated rapamycin every other day (cohort 1) showed the largest reduction in colorectal polyp burden (−39.4 percent; p=0.28), duodenal polyp burden (−33.33 percent; p=0.04), and total polyp burden (−38.6 percent; p=0.26).

By 12 months, patients who received the daily-every-other-week dosing (cohort 2) had the largest decrease in colorectal polyp burden (−29.3 percent; p=0.37) and total polyp burden (−26.3 percent; p=0.29).

Compared with daily dosing (cohort 3), intermittent dosing (cohorts 1 and 2) was associated with significantly reduced duodenal polyp burden at 6 months (p=0.04) and total polyp burden at 12 months (p=0.05).

Based on the present data, encapsulated rapamycin 0.5 mg daily at every-other-week schedule will be evaluated in a phase III trial.