My post to this blog that was written yesterday indicated that for certain men the early use of chemotherapy (docetaxil) could provide significant life extending benefits, especially for men with very advanced prostate cancer. For the purpose of clarification, in this case early use means in men who are still hormone responsive.
Given that chemotherapy is only approved for men who were no longer hormone responsive, or castrate resistant, this could be a game changer for the treatment of men with metastatic prostate cancer. I indicated that this could open up a whole new potential world of rescheduling treatments, new protocols as well as the possibility of combining treatments with chemotherpy.
As I think about this I come to the conclusion that besides doing good research and seeing which combinations could work to extend survival, we need to remain aware that some drugs, particularly toxic chemotherapy drugs like docetaxil should not be combined with other drugs.
This concern is driven home because there has been prior research that shows that docetaxel (Taxotere) is amplified when used with CYP17 inhibitors like ketoconazole and Zytiga.
A clinical study of docetaxel multi-dosed at 100 mg/m(2) and 200 mg ketoconazole result in a 100% increase docetaxel activity and an increased incidence of febrile neutropenia. In another study, concomitant ketoconazole increased docetaxel exposure 160% with 1,200 mg daily, 60% with 800 mg daily and approximately 30% to 50% with 600 mg daily.
A trial using weekly docetaxel and ketoconazole resulted in increased docetaxel exposure by 160% with 1,200 mg daily, 60% with 800 mg daily and approximately 30%-50% with 600 mg daily.
Docetaxil is a toxic drug, it is designed to kill cells and it does not discriminate between normal, healthy cells and cancer cells. Amplifying its effects will cause severe side effects and possible kill the individual. Granted, killing the su
Trials evaluating the early use of chemotherapy with other existing approved drugs will need to be done with very careful and specific management. This management will include reduce dosing and closely monitor subjects.
Actually, the product insert in docetaxil recommends a 50% decrease in dosing when used in combination with ketoconazole. It also recommends avoiding combinations with all CYP3A4 potent inhibitors like Zytiga.
So, as I said yesterday the use of early docetaxel opens up the potential for a new protocols for treatment of men who are still hormone responsive, however any such trials must proceed with careful thought and consideration. Amplified dosages of docetaxil will kill the cancer, but it will also kill the man. Idon’t believe that this is consistent with our overall goals.
Joel T Nowak, M.A., M.S.W.