Influence of concurrent medications on outcomes of men with prostate cancer included in the TAX 327 study

Abstract

The TAX 327 trial was pivotal in establishing docetaxel in castration refractory metastatic prostate cancer. Various commonly prescribed and over-the-counter co-administered medications are thought to exhibit anti-neoplastic properties and/or could potentially have pharmacokinectic interactions with docetaxel lessening the effectiveness of chemotherapy. To examine the effect of on prostate cancer outcomes within this trial, we examined overall survival, prostate-specific antigen (PSA) response, percent PSA reduction, pain response and QOL responses for 14 families of medications including metformin, digoxin, verapamil, proton pump inhibitors, nitrates, statins, cox-2 inhibitors, warfarin, heparins, ascorbic acid, selenium, tocopherol, antidepressants and erythropoietin. Our findings did not reveal any medication that had a significant additive or synergistic effect with docetaxel. We did note, however, that patients on digoxin or verapamil had poorer overall survival, possibly due to a trend of fewer cycles of administered chemotherapy being administered to the verapamil group, consistent with a pharmacokinectic interaction. These data are only hypothesis-generating given the statistical limitations, but may form a basis for similar future analysis in other malignancies. The data suggest the need to be aware of pharmacokinectic interactions with medications that may interact with docetaxel.