Evaluating the value of number of cycles of docetaxel and prednisone in men with metastatic castration-resistant prostate cancer

Abstract

Background: The optimal number of 3-wk docetaxel plus prednisone (DP) cycles for metastatic castration-resistant prostate cancer (mCRPC) is unclear.

Objective: A retrospective analysis of two clinical trials was performed to evaluate the association of the number of cycles with overall survival (OS).

Design, setting, and participants: An exploratory analysis compared outcomes of 332 men who received DP in the TAX-327 trial, which stipulated up to 10 cycles, and 220 men who received DP in CS-205, a randomized phase 2 trial comparing DP plus AT-101 (bcl-2 inhibitor) versus DP plus placebo, which allowed up to 17 cycles.

Measurements: Patients who completed 10 cycles of DP without progression in both trials were included. Men in both arms of CS-205 were combined for analysis, as no significant differences in outcomes were observed. OS was estimated from the date of cycle 10 docetaxel infusion.

Results and limitations: The number of men receiving 10 cycles was similar (p=0.26) in the two trials (166 [50.0%] in TAX-327 vs 99 [45.0%] in CS-205; the latter group received a median of five additional cycles). Six- and 12-mo estimated survival after cycle 10 was 92.2% (95% confidence interval [CI], 86.9-95.4%) and 74.6% (CI, 67.2-80.5%) in TAX-327, compared with 92.8% (CI, 85.5-96.5) and 63.4% (CI, 51.8-72.9%) in CS-205. Subanalyses suggested that <10 cycles may have a negative impact and prostate-specific antigen (PSA) declines at cycle 10 may carry a favorable impact. The significance of continued PSA declines up to 17 cycles is unclear. Limitations of a retrospective analysis apply.

Conclusions: A survival benefit was not detected with >10 cycles of DP in men with mCRPC in this retrospective hypothesis-generating analysis.

Fig. 1

Study schema. DP = docetaxel plus prednisone; Q3 wk = every 3 wk; PSA = prostate-specific antigen; PD = progressive disease.

Fig. 2

Overall survival (a) from day 1 of cycle 10 and beyond day 90 for those with and without ≥30% prostate-specific antigen (PSA) decline by day 90, (b) for those with and without PSA decline from cycle 9 to cycle 10, and (c) for those with and without ≥30% PSA decline by day 90.

Fig. 3

Proportion of patients with declining prostate-specific antigen (PSA) by cycle of treatment. Bars represent proportion of patients among those remaining on study treatment, and lines represent the proportion of patients (the denominator being the overall number of patients who received any docetaxel-prednisone therapy on the trial) who received further docetaxel and prednisone study treatment beyond a given cycle.