[Final Results of a Phase Ib/IIa Study of Phenoxodiol in Hormone-Refractory Prostate Cancer -- AACR/EORTC]
>>Abstract C96
Final Results of a Phase Ib/IIa Study of Phenoxodiol in Hormone-Refractory
Prostate Cancer
Robert Davies,1 Alastair Tulloch,2 Mark Frydenberg,3 Graham
Kelly.4 Sir Charles Gairdner Hospital,1 Perth, Australia, St John of God Hospital,2 Perth,
Australia, Monash Medical Center,3 Melbourne, Australia, Marshall Edwards Inc,4 Sydney,
Australia.
Introduction:
Phenoxodiol (PXD) is a novel anti-cancer agent that is being developed in the oral dosage form as second-line therapy for hormone-refractory, docetaxel-refractory prostate cancer (HRDRPC), as third-line therapy for refractory ovarian cancer patients, and as a chemo-sensitizer of carboplatin in renal carcinoma. The primary biochemical target of phenoxodiol is the sphingosine kinase-Akt signaling pathway, resulting in induction of apoptosis in prostate cancer cells through blockage of the phosphorylation of the anti-apoptotic factors, XIAP and FLIPshort. We report here on a study in 26 men with metastatic, hormone-refractory prostate cancer, where a primary objective was to establish if the oral dosage form of PXD would have an antitumor effect in these patients, and to determine an appropriate dose to take into a Phase 2 study in patients with HRDRPC.
Methods:
PXD was given 8-hourly for 3 consecutive weeks each month for 6 months. There were 4 dose strata - 20, 80, 200 and 400 mg. The age of the subjects was mean 70.1 years (range 55-85), the Gleason score was mean 8.04 (range 6-9), and the baseline PSA level was mean 56.3 (range 7-118). Time to clinical progression (TTCP)- the time at which the clinician deemed that the patient was no longer responding to treatment- was measured in weeks and the number of patients with a PSA response (50% or greater reduction in PSA levels from baseline) was calculated for each group.
Results:
PXD provided a significant delay in disease progression in this group of patients with advanced prostate cancer. The effect was dose-dependent, with the 200 mg and 400 mg dosages showing a significant improvement in both the time to clinical progression and the incidence of PSA response compared to the 20 and 80 mg dosages. No drug-associated toxicities were reported.
Conclusions:
The oral dosage form of phenoxodiol produced a significant antitumor effect in late-stage, hormone refractory prostate cancer, providing a significant delay in tumor progression at a dosage of 200 or 400 mg 8-hourly. This effect was achieved without toxicity.
Table 1 TTCP (weeks) and PSA reponse by group
Dose n TTCP PSA-R No. 16wks 24wks 36wks 48wks
20 6 13 0 of 17% 17% 0% 0%
80 6 17 0 Pts 50% 0% 0% 0%
200 6 43 1 on 67% 67% 33% 33%
400 5 34* 2 Rx 88% 80%* 40%* 40%*
*3 patients are continuing treatment (20 weeks) <<
Cheers, Tuck |
