Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer

Department of Medical Oncology and Hematology, Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada.
New England Journal of Medicine (Impact Factor: 55.87). 10/2004; 351(15):1502-12. DOI: 10.1056/NEJMoa040720
Source: PubMed


Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease.
From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone.
As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel.
When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

Download full-text


Available from: Nicholas D James,
  • Source
    • "p = 0.0006). This is in strong contrast to the usage of docetaxel as second line therapeutic in patients with CRPC, where only a mean OS improvement of 2–3 months could be achieved [16] [17]. Effective treatment of advanced prostate cancer remains very challenging and much effort has to be undertaken to further understand the mechanisms of resistance. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Androgen deprivation therapy (ADT) is considered as the standard therapy for men with de novo or recurrent metastatic prostate cancer. ADT commonly leads to initial biochemical and clinical responses. However, several months after beginning of treatment tumors become castration-resistant and virtually all patients show disease progression. At this stage, tumors are no longer curable and cancer treatment options are only palliative. In this review, we describe molecular alterations in tumor cells during ADT, which lead to deregulation of different signalling pathways and castration-resistance, and how they might interfere with the clinical outcome of different second-line therapeutics. A recent breakthrough finding that early chemotherapy is associated with a significant survival benefit in metastatic hormone-sensitive disease highlights the fact that there is time for a fundamental paradigm shift in the treatment of advanced prostate cancer. Therapeutic intervention seems to be indicated before a castration-resistant stage is reached to improve therapeutic outcome and to reduce undesirable side effects. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
    Cancer letters 07/2015; 367(1). DOI:10.1016/j.canlet.2015.06.021 · 5.62 Impact Factor
  • Source
    • "The drivers of prostate cancer cell proliferation, metastasis, and evasion of apoptosis include activation of the androgen receptor, carcinogenic signaling within cells, and the effect of survival signals from the microenvironment. Regression or stabilization of cancer burden occurs in some CRPC patients through the use of hormonal therapy [2] [3], cytotoxic therapy [4] [5], and immune-based therapy [6] that abrogates one or more of these drivers. An alpha-emitting radiopharmaceutical [7] is also currently used clinically in CRPC patients with skeletal metastases to prolong overall survival and localized radiation cell killing in bone metastases. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Preclinical xenograft models have contributed to advancing our understanding of the molecular basis of prostate cancer and to the development of targeted therapy. However, traditional preclinical in vivo techniques using caliper measurements and survival analysis evaluate the macroscopic tumor behavior, whereas tissue sampling disrupts the microenvironment and cannot be used for longitudinal studies in the same animal. Herein, we present an in vivo study of [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) designed to evaluate the metabolism within the microenvironment of LAPC4-CR, a unique murine model of castration-resistant prostate cancer. Mice bearing LAPC4-CR subcutaneous tumors were administered [(18)F]-FDG via intravenous injection. After a 60-minute distribution phase, the mice were imaged on a PET/CT scanner with submillimeter resolution; and the fused PET/CT images were analyzed to evaluate tumor size, location, and metabolism across the cohort of mice. The xenograft tumors showed [(18)F]-FDG uptake that was independent of tumor size and was significantly greater than uptake in skeletal muscle and liver in mice (Wilcoxon signed-rank P values of .0002 and .0002, respectively). [(18)F]-FDG metabolism of the LAPC4-CR tumors was 2.1 ± 0.8 ID/cm(3)*wt, with tumor to muscle ratio of 7.4 ± 4.7 and tumor to liver background ratio of 6.7 ± 2.3. Noninvasive molecular imaging techniques such as PET/CT can be used to probe the microenvironment of tumors in vivo. This study showed that [(18)F]-FDG-PET/CT could be used to image and assess glucose metabolism of LAPC4-CR xenografts in vivo. Further work can investigate the use of PET/CT to quantify the metabolic response of LAPC4-CR to novel agents and combination therapies using soft tissue and possibly bone compartment xenograft models. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Translational oncology 06/2015; 63(3). DOI:10.1016/j.tranon.2015.03.004 · 2.88 Impact Factor
  • Source
    • "However, most patients progress to castration-resistant prostate cancer (CRPC) at varying intervals following ADT [2]. For such patients, docetaxel (DCT)–based chemotherapy has been established as first-line treatment [3] [4]. More recently, new classes of treatments, such as second-line taxane cytotoxic agent [5], androgen-targeted therapies [6] [7], or immunotherapy [8], have been approved for patients with CRPC following DCT-based chemotherapy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To identify pretreatment prognostic factors for patients with castration-resistant prostate cancer (CRPC) undergoing docetaxel (DCT) chemotherapy. We retrospectively analyzed 102 patients with CRPC who underwent DCT chemotherapy (dosage: 60-75mg/m(2)) from December 2001 to August 2013. The parameters evaluated as prognostic factors were as follows: age, body mass index, Gleason score, clinical TNM stage, prior radical prostatectomy, prior radiation therapy, performance status, presence of pain, laboratory results at the start of DCT, and prostate-specific antigen (PSA) kinetics during prior androgen deprivation therapy (ADT), including PSA level at the start of ADT (PSA-ADT), PSA half-time (PSAT1/2), time to nadir, PSA level at nadir (PSA-Nadir), duration of nadir, PSA doubling time (PSADT), and PSA level at the start of DCT (PSA-DCT). Univariate and multivariate analyses were performed to identify independent prognostic factors. Median cancer-specific survival (CSS) duration following CRPC diagnosis was 28.0 months. In univariate analyses, performance status, serum albumin, serum creatinine, PSAT1/2, time to nadir, PSA-Nadir, duration of nadir, PSADT, and PSA-DCT showed a potential association with prognosis (P<0.001-0.077). Multivariate analyses of these parameters showed that performance status (hazard ratio [HR] = 0.046; P = 0.046), serum creatinine (HR = 3.028; P = 0.036), PSAT1/2 (HR = 0.172; P = 0.007), PSA-Nadir (HR = 4.884; P = 0.033), PSADT (HR = 0.148; P<0.001), and PSA-DCT (HR = 5.222; P = 0.004) remained independent predictors of CSS in CRPC. PSA kinetic parameters measured during prior ADT are significant surrogate markers predicting CSS in patients undergoing DCT chemotherapy for CRPC. Copyright © 2015 Elsevier Inc. All rights reserved.
    Urologic Oncology 02/2015; 33(5). DOI:10.1016/j.urolonc.2015.01.017 · 2.77 Impact Factor
Show more