4505 Background: S9916 was designed to compare two regimens: mitoxantrone/prednisone (M+P) vs docetaxel/estramustine (D+E), in patients (pts) with HRPC. Stratification factors were: Progression type: inmeasurable/ evaluable disease vs increasing PSA only; NCI CTC Bone pain scale: Grade ≥ 2 vs < 2; and SWOG performance status 0–1 vs 2–3. The primary endpoint was survival. 770 pts were accrued. There were 406 deaths. Methods: Baseline, treatment and follow-up data were compiled for a subset of 499 pts who had a minimum of two PSAs recorded in the first 3 months on-study. 161 (32.3%) had a prior radical prostatectomy. We used Cox regression analysis to test whether PSA velocity was a prognostic factor for mortality independent of treatment (M+P vs D+E) received, adjusting for influential baseline variables. All statistical tests were 2-sided. Results: Initial PSA and prior prostatectomy were associated with mortality and included in all analyses. In an analysis without treatment, PSA velocity was correlated with survival (HR=3.67; 95% CI=(2.72,4.96), p<.0001), with odds of failing nearly quadrupling with a unit increase in PSA velocity. Without adjusting for PSA velocity, treatment was associated with mortality failure rate (HR = 1.39 for M+P vs. D+E, 95% confidence interval (CI)=(1.10,1.75), p=.006). After adjustment for PSA velocity, treatment was no longer associated with mortality (HR = 1.15 for M+P vs. D+E, 95% CI=(.91,1.46), p=.23), while PSA velocity was still significant (HR = 3.56, 95% CI=(2.62,4.83), p<.0001). Patients with a prior prostatectomy had a failure rate nearly half that for patients without prior prostatectomy (HR=.55, 95% CI=(.42,.72), p<.0001), and HR that less than doubled with a unit increase in PSA velocity (HR=1.69, 95% CI=(1.02,2.79), p=.0003). Conclusions: PSA velocity measured during the first 3 months of chemotherapy provides independent prognostic information to treatment and should be further investigated as a surrogate endpoint for mortality in future trials of chemotherapeutic regimens for HRPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis National Institutes of Health; TAP Pharmaceutical Co.; Aventis Pharmaceutical Co.
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Crawford et al. (2004) studied this question.