OncoGenex Technologies Inc. has announced that the company's lead cancer drug candidate, OGX-011, also referred to as custirsen, was well-tolerated in combination with either docetaxel or mitoxantrone administered as second-line chemotherapy in patients with hormone refractory prostate cancer.
Additionally, patients treated with second-line chemotherapy plus OGX-011 showed ongoing survival durations better than results published with chemotherapy alone. Phase 2 data were presented today at the 2008 Genitourinary Cancers Symposium. OncoGenex and Isis Pharmaceuticals, Inc. are collaborating on development of OGX-011. According to data presented by Dr Fred Saad, Professor of Surgery/Urology at the University of Montreal, the primary objectives of safety and tolerability were achieved in the 42 patients evaluated in the study. In addition, encouraging outcomes were observed with OGX-011 administered in combination with second-line chemotherapy.
More chemotherapy than expected was safely administered to and tolerated by patients when OGX-011 was combined with second-line chemotherapy: Patients received a median of 6 cycles of mitoxantrone or 7.5 cycles of docetaxel as second-line chemotherapy. These data compare favourably with published reports documenting a median of 3-4 cycles with second-line chemotherapy alone.
Survival was better than expected based on previously published reports: With a median follow-up of 13.3 months following second-line chemotherapy, approximately 30 per cent of patients in both arms have not manifested disease progression and approximately 60 percent of patients remain alive in both arms. Median survival has not been reached in either arm. These data compare favourably with published results documenting median survivals of approximately 10 months.
Reduction in pain or analgesic use was achieved in 50 per cent or more of patients entering the study with pain: Reductions in pain or analgesic use were seen in 50 per cent of evaluable patients treated with mitoxantrone and in 67 per cent of evaluable patients retreated with docetaxel.
This phase II study was designed as an open-label, randomized, multicenter study evaluating weekly administration of OGX-011 in combination with second-line chemotherapy in patients with metastatic hormone refractory prostate cancer who were previously treated with a minimum of 2 cycles of docetaxel-based first-line chemotherapy. Patients in this study represented a poor prognostic population due to rapid disease progression after completing first-line docetaxel therapy with a median of 0.7 months in the mitoxantrone treated group or 2.1 months in the docetaxel retreated group. Because OGX-011 has been shown to enhance chemotherapy and reverse chemotherapy resistance in preclinical in vitro and in vivo models, the aim of this study was to assess the effect of OGX-011 in combination with either mitoxantrone or docetaxel re treatment as second-line chemotherapy. Phase III studies are planned utilizing chemotherapy plus OGX-011 as second-line therapy in patients progressing after a first-line docetaxel regimen.
"These data show that the combination of OGX-011 with docetaxel or mitoxantrone may improve treatment outcomes in second-line prostate cancer," said Dr. Fred Saad, who is also the primary investigator in the study. "The data also suggests that re treatment with docetaxel when combined with OGX-011 may reverse chemotherapy resistance in second-line docetaxel re treatment. We look forward to confirming these data in planned phase III studies".
OGX-011 is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer indications and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Increased cluster in production is observed in many human cancers, including prostate, non-small cell lung, breast, ovarian, bladder, renal, pancreatic, anaplastic large cell lymphoma and colon cancers and melanoma. Increased clusterin production is linked to faster rates of cancer progression, treatment resistance and shorter survival duration.