4705 Background: Taxane (T) based chemotherapy improves survival in patients (pts) with progressive CMPC. A high frequency of non-cancer related factors places this group at risk for toxicities which can result in dose reductions and treatment delays that may compromise overall outcomes. We explored associations between age, baseline characteristics and co-morbidities and the ability to administer chemotherapy in CMPC. Methods: We evaluated the delivered chemotherapy to 108 sequentially treated men enrolled on clinical trials for progressive CMPC treated with T or Epothilone (E) based regimens. Multi-variate analysis was performed to determine the predictors of dose reduction, delay or discontinuation of therapy due to toxicity. Studied were: age, Charlson Co-Morbidity, stage at diagnosis, Gleason grade, Karnofsky performance status (KPS), extent of disease, and baseline biochemical parameters. Results: The median age was 68 (range 52–84), KPS: 90 (range 70–90); PSA 95 ng/ml (range .5–1923 ng/ml), HGB 12.7 g/dl (range 8.2–15.7g/dl), Gleason 8 (range 4–10) Tumor 3 (range 1–4) of whom 66 (61%) received a T, 42 (39%) E, and 19% had significant co-morbidities (cardiovascular, diabetes or gastrointestinal). For the overall group dose reductions were seen in 52%, delays in 56%, and 44% discontinued therapy prematurely after a median of 5 (range 1 to 16) cycles. Most common reason to delay or reduce chemotherapy was leukopenia in 31%, and neurotoxicity in 19%. Significant associations existed with dose reduction (P<0.0001), delay (P=0.0039) or discontinuation (P=0.0082) depending on either T or E administered. Initial M stage (P=0.03) and age (0.09) trended to predict for discontinuing therapy. There was no association between co-morbidities and other baseline parameters to predict dose reduction, delay or discontinuation of chemotherapy. Conclusions: Toxicities requiring dose modifications occur frequently in pts with progressive CMPC treated with T based chemotherapy. The toxicities were regimen specific, and did not appear to be related to co-morbidities in a patient group that met the eligibility criteria for Phase II clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis