(ChemotherapyAdvisor) – Intravesical administration of the second-generation antisense oligonucleotide OGX-27 has shown activity against bladder cancer, results of a phase 1 study presented at the 2012 Genitourinary Cancers Symposium have shown.

OGX-427, which potently inhibits Heat Shock Protein 27 (Hsp27), a cytoprotective protein, was found to be well tolerated with minimal toxicity, according to Alan I. So, MD, of the Vancouver Prostate Centre, Vancouver, BC, Canada, and colleagues.

“Interestingly, the complete response rate observed to date is higher than expected,” said Dr. So. Of 15 patients treated with OGX-427, 33% had complete responses with no pathologic evidence of disease in postsurgical tissue following four doses of OGX-427 administered intravesically over an 8-day period.

Patients with Ta, T1, or carcinoma-in-situ who were candidates for transurethral resection of the bladder tumor or those with muscle invasive bladder cancer (>cT2) and candidates for radical cystectomy received intravesical OGX-427 on days 1, 3, 5, and 8; surgery was performed days 9–12. After tolerability and safety were assessed in each cohort, the dose was escalated. Planned dose levels are 20uM, 50 uM, 100uM, 250uM, 500uM, and 750uM.

No dose-limiting toxicities have been observed and no significant adverse events reported. One patient developed grade 1 gross hematuria within 24 hours of OBX-427 administration that resolved spontaneously, the investigators reported.

“We will continue enrolling additional patients with larger tumors and continue to evaluate the effect of higher OGX-427 doses on Hsp27 levels,” said Dr. So.

The 2012 Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and the Society of Urologic Oncology.

OGX-427 is being developed by OncoGenex Pharmaceuticals, Inc.

Abstract

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