Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer

Summary Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5–913.7). Median duration of therapy was 6.5 months (2.6–14.0). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of