A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer

Abstract

Purpose: To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC).

Patients and methods: A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Primary end point was overall survival, and secondary end points were events progression-free survival (PFS), response rate, response duration. Quality of life (QoL) was also assessed in both treatment groups.

Results: The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46-0.86). Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease) were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155). Pain response rate was higher in D3P arm (61.11%, P = 0.0011) than in M3P (23.08%) arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm.

Conclusions: Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain.

Trial registration: clinicaltrials.gov NCT00436839.

Conflict of interest statement

Competing Interests: The investigators of this clinical trial received funding from Sanofi-Aventis for recruiting patients and conducting this clinical trial. The scientific results of the clinical trial were shared by all the co-authors and Sanofi-Aventis. However, the co-authors had no relevant connection to products in development or marketed products of Sanofi-Aventis. The co-authors have declared that no competing interests exist, and they have adhered to all PLOS ONE policies on sharing data and materials.

Figures

Figure 1. CONSORT diagram.

Figure 2. Kaplan-Meier curve for overall survival by different treatment arms in the intention to treat analysis.

The Kaplan-Meier curve for D3P arm was above the curve for M3P arm, log-rank analysis proved this difference was statistically significant (P = 0.0011, HR = 0.63, 95% CI [0.46–0.86]). D3P = docetaxel plus prednisone arm. M3P = mitoxantrone plus prednisone arm.

Figure 3. The primary analysis on overall survival in subgroups.

Patients in D3P arm and M3P arm were divided into subgroups by stratification variables (baseline PPI and KPS) and prognostic factors of interest (age, baseline PSA and visceral involvement). There were no statistically difference between two arms in subsets of PPI≥2，KPS≥80，median PSA