Imagine biting into one of south Texas’s most inviting sweets, a pecan pie, but with all the pecans still in their shells—not only insipid, but potentially dangerous. At the 2003 San Antonio Breast Cancer Symposium (San Antonio, TX, December 3-6, 2003), my heart sank when I learned that the activity of tamoxifen was almost completely inhibited when paroxetine was coadministered—a pairing I so frequently used for control of vasomotor symptoms. The purpose of this article is to review one small segment of the rapidly expanding understanding of adverse drug interactions, namely the interaction of tamoxifen with selective serotonin-reuptake inhibitors (SSRIs) that may block any therapeutic benefit.
To further refine predictors of resistance to docetaxel, they subsequently evaluated the molecular patterns of the residual tumors after 3 months of docetaxel and found these patterns amazingly similar despite initial sensitivity or resistance. Plasma levels of drugs and metabolites were measured. Cyclophosphamide is a prodrug and must be activated by CYP3A. Thus, patients who had higher levels of the parent, inactive cyclophosphamide were those patients who had less active forms of CYP3A.
The future is exciting with the possibility of developing truly customized, 100%-effective therapies for our patients. For the present, however, besides entering our patients onto well-designed clinical trials asking important questions, we must not encumber our currently available therapies with combinations of drugs that effectively make them a placebo.