(ChemotherapyAdvisor) – The oral small-molecule galeterone (TOK-001) was safe and led to a decline in prostate-specific antigen (PSA) expression in chemotherapy-naïve patients with castration-resistant prostate cancer (CRPC), results of a Phase I trial presented during the AACR Annual Meeting 2012 in Chicago, IL, have found.

Galeterone, a semi-synthetic steroid analog, is known to inhibit CYP17 lyase activation, bind and inhibit the androgen receptor, and degrade androgen receptor protein. The dose-escalation ARMOR1 study enrolled 49 men ages 48 to 93 years with metastatic and nonmetastatic CRPC that had progressed during androgen ablation therapy. Patients were randomized to one of eight dose-escalation cohorts in which galeterone capsules were administered in daily single or split oral doses of 650mg, 975mg, 1,300mg, 1,950mg, or 2,600mg for 12 weeks.

At 12 weeks, the maximum tolerated dose was not reached. Overall, 58% of patients had grade 1 adverse events (AEs) and 30%, grade 2. The most commonly reported AEs were fatigue (36.7%), increase in aspartate aminotransferase (32.7%), increase in alanine aminotransferase (30.6%), nausea (28.6%), diarrhea (26.5%), and pruritus (24.5%). In 15 patients, grade 2 and 3 transient elevations of liver function tests (LFT) were observed, the majority asymptomatic. Of these, 11 patients underwent drug interruptions; 6 of 7 were successfully rechallenged and returned to treatment with no recurring ≥grade 3 LFT elevations.

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Nine serious AEs were reported, eight unrelated to galeterone. One patient had grade 4 rhabdomyolysis in the setting of simvastatin 40mg qd and underlying renal insufficiency. No events of adrenal mineralocorticoid excess were observed.

Of the 49 patients, 24 (49%) had >30% maximal PSA reductions, including 11 (22%) with >50% maximal PSA reductions. In addition, CT scans revealed reduction in tumor size for some patients.

The manufacturer, Tokai Pharmaceuticals (Cambridge, MA), has planned a Phase 2 study later this year to explore the long-term safety and efficacy of galeterone.