A total of 42 taxane-resistant prostate cancer patients with progressive (metastatic) disease were enrolled into the clinical trial at 7 dose levels. As previously reported, 28 (67%) reached the first reassessment (two 28-day cycles); 15 (54%) of these had stable disease or improvement of metastatic soft tissue and/or bone lesions by imaging and have received 1 to 8 additional treatment cycles before disease progression. These include patients who are taxane resistant and who failed prior hormonal, chemotherapy and/or experimental forms of therapy including Abiraterone?® and MDV-3100. Prior treatment with ketoconazole (41.5% of patients) had no effect on the activity of Apoptone to stabilize disease. The drug was well tolerated at all doses with no overt dose-limiting toxicities observed. 

The Kaplan-Meier estimate (1) for the median time to progression in evaluable taxane-resistant patients was 16 weeks (range 8-24) in this trial. Due to early signs of activity, the 20 mg dose group was expanded to include 14 patients for whom the data are complete. Eleven of these were evaluable with an actual median time to progression of 20 weeks (range 8-28). At the initiation of therapy, Apoptone induced a disease flare in some patients, which can be mistakenly interpreted as disease progression. Progression was assessed by the Prostate Cancer Working Group 1 (PCWG1) criteria, which does not account for disease flares. Disease flares are not uncommon at the initiation of therapy for metastatic prostate cancer.

"Use of PCWG1 response criteria appears to lead to an underestimation of the TTP in the taxane-resistant patients in this dose escalation study," explained Dwight R. Stickney, M.D., Chief Medical Officer of Harbor BioSciences. "Consequently, the pre-chemotherapy patients are evaluated for progression with the PCWG2 response criteria, which accounts for disease flares. We believe 19 of the 42 patients may have been prematurely removed from the study without confirmation of disease progression, as required by the PCWG2 recommendations."

Overall Patients (Both Groups)

Antitumor effects were noted in all doses studied including the lowest dose. In some individuals, there have been responses in bone scans ranging from decrease of tracer uptake to resolution of some bone tumors.