Fast track — ArticlesPrednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial
Introduction
Prostate cancer is the second most common cause of cancer death in men in the USA1 and the third most common cause of death in developed countries.2 For patients with metastatic prostate cancer, androgen deprivation therapy improves symptoms, but patients invariably develop progressive disease.3 On the basis of an improvement in survival compared with mitoxantrone plus prednisone in patients with metastatic castration-resistant prostate cancer,4, 5, 6 docetaxel in combination with prednisone is standard first-line chemotherapy in this setting. No treatment has been approved by the US Food and Drug Administration, however, for patients whose disease progresses after docetaxel treatment. Mitoxantrone is often administered because of its favourable effects on quality-of-life outcomes.7, 8 However, no intervention improves survival in this disease setting.
Cabazitaxel (XRP6258; TXD258; RPR116258A) is a tubulin-binding taxane drug as potent as docetaxel in cell lines.9 Additionally, the drug has antitumour activity in models resistant to paclitaxel and docetaxel.10, 11 Phase 1 and 2 clinical studies have shown that neutropenia is the primary dose-limiting toxicity, and the recommended phase 2 doses were 20 and 25 mg/m2, with antitumour activity in solid tumours including docetaxel-refractory metastatic castration-resistant prostate cancer.12, 13 We undertook a randomised, multicentre, multinational, phase 3 trial (EFC6193; TROPIC) with the aim of assessing whether cabazitaxel plus prednisone improves overall survival compared with mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer who had progressed after docetaxel-based chemotherapy.
Section snippets
Patients
This randomised open-label phase 3 study was undertaken at 146 centres in 26 countries. Patients had pathologically proven prostate cancer with documented disease progression during or after completion of docetaxel treatment. Eligible patients were aged at least 18 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients who had previous mitoxantrone therapy, radiotherapy to 40% or more of the bone marrow, or cancer therapy (other than
Results
Between Jan 2, 2007, and Oct 23, 2008, 755 patients were randomly assigned to treatment groups (378 cabazitaxel and 377 mitoxantrone; figure 1). The treatment groups were well balanced at baseline with respect to demographic and disease characteristics and previous treatments (table 1). Roughly 50% of patients had measurable soft-tissue disease and 25% had visceral (poor prognosis) disease. The median dose of docetaxel received before the study was 576·6 mg/m2 (IQR 408·4–761·2) in the
Discussion
Cabazitaxel is the first drug to improve survival in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment, resulting in a 30% reduction in the risk of death and an improved median overall survival compared with mitoxantrone (panel). Currently, these patients have few therapeutic options, with no treatment able to prolong survival in this setting. The analysis of survival in subgroups defined by prognostic factors supports the
References (20)
- et al.
Update on tubulin binding agents
Pathol Biol (Paris)
(2006) - et al.
A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients
Ann Oncol
(2008) The McGill Pain Questionnaire: major properties and scoring methods
Pain
(1975)- et al.
Cancer statistics, 2009
CA Cancer J Clin
(2009) Global cancer facts and figures 2007
- et al.
A re-evaluation of nonhormonal cytotoxic chemotherapy in the treatment of prostatic carcinoma
J Clin Oncol
(1985) - et al.
Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer
N Engl J Med
(2004) - et al.
Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer
N Engl J Med
(2004) - et al.
Quality of life and pain in advanced stage prostate cancer: results of a Southwest Oncology Group randomized trial comparing docetaxel and estramustine to mitoxantrone and prednisone
J Clin Oncol
(2006) - et al.
Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone
Cancer
(2007)
Cited by (2798)
Novel solid self-emulsifying drug delivery system to enhance oral bioavailability of cabazitaxel
2024, International Journal of PharmaceuticsOral Toxicities of PSMA-Targeted Immunotherapies for The Management of Prostate Cancer
2024, Clinical Genitourinary CancerProstate Cancer and Malignant Ascites: The Mayo Clinic Experience With a Rare and Aggressive Disease Progression
2024, Clinical Genitourinary Cancer