Once we have failed docetaxel therapy (chemo therapy) we have very few options available to control advanced prostate cancer. There is a recnt report about a clinical trial using a new potential drug, Patupilone. Patupilone has shown some evidence that it exhibits a limited positive effect in the pre-clinical setting in taxane resistant models of prostate cancer, meaning prostate cancer that does not respond or no longer responds to taxotere therapy.
Patupilone belongs to a new class of agents that works by preventing the growth of cancer cells. Patupilone kills cancer cells by attacking the cell’s internal structures, microtubules. Microtubules have many functions in cells, including forming an internal type of skeleton at the cellular level.
At the current ASCO conference, E. K. Beardsley, MD, presented the results of a
multi-center, Phase II study which enrolled castrate resistant prostate cancer patients (CRPC) who failed docetaxel (chemotheray) within 6 months of their recruitment. The men were given patupilone at a dosage of 10mg/m2 every three weeks.
We all know that drug resistance mechanisms will eventuly reduce response rate and response duration in men with castration-resistant prostate cancer (CRPC) receiving docetaxel-based therapy (chemo-resistants) (chemo-therapy failure). It is believed that Patupilone may be unaffected by some of the resistance mechanisms and remain effective even after Taxotere stops working. Therefore, a phase II study was designed to assess the safety and activity of patupilone in CRPC patients with and without previous chemotherapy (phase I/II).
A dose reduction to 8 mg/m2 was necessary after the first 6 patients were treated due to gastro-intestinal (GI) toxicity. A PSA decline of > 50% was the primary endpoint in the study. Eighty three (83) patients with a median time to progression of 1 month after docetaxel were enrolled in the study. Of the 78 evaluable patients, PSA declines of >30% and >50% were observed in 56% and 45% of patients respectively. Improvement in pain was also noted in 51% of patients eligible for analysis. The 8mg/m2 dose was well tolerated.
The researchers have concluded that the PSA responses and tolerability with this regimen merit further investigation of the efficacy of patupilone in the treatment of hormone and chemo resistant prostate cancer. Even if t turns out that patupilone does not extend life, it would be good o have available a new drug that might control pain without the side effects of the ore traditional narcotic based pain killers that are currently used.
FYI- There is currently recruiting another randomized multicenter phase II trial of Patupilone (EPO906) plus prednisone versus docetaxel (taxotere) plus prednisone in patients with metastatic hormone refractory prostate cancer to evaluate if perhaps patupilone is a better first line chemo drug than docetaxel.
Joel T Nowak MA, MSW