Open-label, phase I dose-escalation study of sodium selenate, a novel activator of PP2A, in patients with castration-resistant prostate cancer.
BACKGROUND
Angiogenesis is fundamental to the progression of many solid tumours including prostate cancer. Sodium selenate is a small, water-soluble, orally bioavailable activator of PP2A phosphatase with anti-angiogenic properties.


METHODS
This was a dose-escalation phase I study in men with asymptomatic, chemotherapy-naïve, castration-resistant prostate cancer. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included establishing the safety, tolerability and pharmacokinetic profile.


RESULTS
A total of 19 patients were enrolled. The MTD was 60 mg per day. Dose-limiting toxicity (fatigue and diarrhoea) was observed at 90 mg per day. The most frequently reported treatment-related adverse events across all treatment cohorts were nausea, diarrhoea, fatigue, muscle spasms, alopecia and nail disorders. No grade 4 toxicities were observed and there were no deaths on study. Linear pharmacokinetics was observed. One patient had a PSA response >50%. Median time to PSA progression (for non-responders) was 14.2 weeks. Mean PSA doubling time increased during the main treatment phase from 2.18 months before trial to 3.85 months.


CONCLUSIONS
Sodium selenate is well tolerated at a dose of 60 mg per day with modest single-agent efficacy similar to other anti-angiogenic agents. Further trials in combination with conventional cytotoxic regimens are warranted.
Corcoran
N M
NM
Department of Surgery, Division of Urology University of Melbourne, Royal Melbourne Hospital, 5th Floor Clinical Sciences Building, Royal Parade, Parkville, Victoria 3050, Australia. niallmcorcoran@gmail.com
Hovens
C M
CM
Michael
M
M
Rosenthal
M A
MA
Costello
A J
AJ
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D054648:Protein Phosphatase 2; D064586:Selenic Acid; D018036:Selenium Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018036:Selenium Compounds; D054648:Protein Phosphatase 2; D064586:Selenic Acid