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

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.