The Canadian Uro‐Oncology Group multicentre phase II study of docetaxel administered every 3 weeks with prednisone in men with metastatic hormone‐refractory prostate cancer progressing after mitoxantrone/prednisone

Abstract

PATIENTS AND METHODSThirty patients from four centres were enrolled in the study; all had had previous MP for symptomatic, metastatic HRPC and all had castrate levels of testosterone maintained during therapy. RESULTSAt enrolment, the median age was 69 years, the mean PSA level was 324 ng/dL, and 86% of patients reported pain. There was a PSA response in 57% of the men and a reduction in pain in > 60%; the overall QoL was maintained. There were four cases of febrile neutropenia and two treatment-related deaths. The median progression-free and overall survival were 5 and 15 months, respectively. CONCLUSIONDocetaxel was associated with high rates of PSA and pain response in this study. Nonhaematological toxicity was similar to that during first-line treatment, but rates of febrile neutropenia and toxic death appeared to be slightly higher. In selected patients with progressive metastatic HRPC previously treated with mitoxantrone, docetaxel appears to be a beneficial therapeutic option. KEYWORDSprostatic neoplasms, drug therapy, docetaxel, mitoxantrone, phase II, pain Study Type -Therapy (individual cohort study) Level of Evidence 2c OBJECTIVETo investigate the use of docetaxel 75 mg/m 2 intravenously every 3 weeks plus prednisone 5 mg orally twice daily in men with metastatic hormonerefractory prostate cancer (HRPC) progressing after first-line mitoxantrone/ prednisone (MP), the primary outcome being progression-free survival with prostatic-specific antigen (PSA) and pain response, toxicity and quality of life (QoL) also assessed.

Three-Weekly Docetaxel With Prednisolone for Patients With Hormone-Refractory Metastatic Prostate Cancer: Preliminary Results

“…In our study, the PSA response rate ≥50% reduction of the base line level was 42.9%. As Shimazui et al 8 , had recorded an overall PSA response rate of 68.8%, our results were highly comparable with Naito et al 21 , Tannock et al 6 (44.4% and 45%, respectively), on the other hands, Saad et al 23 and Ansari J et al 24 , had recorded a higher response rates ( 57% and 54%, respectively ).…”

“…respectively. While, Shimazui et al 8 had reported a median time to disease progression of 8.5 months and median overall survival of 12.5 months, Saad et al 23 had reported a median progression-free and overall survival of 5 and 15 months, respectively and Ansari J et al 24 median treatment-free interval of 24 and median overall survival was 13 months. However, Howard et al 25 , had reported in a Canadian retrospective study that among 161 patients with HRMPC docetaxel and prednisone did not perform as well in terms of median survival, as it was shown to in prior clinical trials (17.22 vs. 18.9 months).…”

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience

“…Further, these median OS are not only greater than that of nine months after treatment with 55 mg/m 2 DTX [12] or that of 18 months after treatment with 60 mg/m 2 DTX in SWOG 9916 but also consistent with the 15-27 months median OS obtained after treatment with 70-75 mg/m 2 DTX [1,4-6,13,14]. The median OS of 24 months or more achieved in this study was considered to be due to the initiation of DTX therapy with low PSA value as compared with that obtained in the previous reports [1,4-6,13,14], because multivariate analysis performed in this study and the report by Bamias et al [15] demonstrated that OS prolonged when PSA was low at the initiation of DTX therapy. Since the adverse events observed in this study were well tolerated, treatment with 60 mg/m 2 DTX seems to be effective and safe even in EMP-refractory CRPC patients.…”

PIAS1 is a crucial factor for prostate cancer cell survival and a valid target in docetaxel resistant cells

“…For treatment of castration resistant prostate cancer (CRPC) a systemic chemotherapy has been developed in the last years [ 1 – 3 ]. The chemotherapeutic drug docetaxel (Taxotere®) is given to patients after androgen deprivation therapy (ADT) failure on the basis of improved overall survival, pain reduction, prostate-specific antigen response, and quality of life [ 3 ].…”