Article

Effect of abiraterone acetate on fatigue in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy

Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
Annals of Oncology (Impact Factor: 6.58). 11/2012; 24(4). DOI: 10.1093/annonc/mds585
Source: PubMed

ABSTRACT Background
Fatigue is a common, debilitating side-effect of prostate cancer and its treatment. Patient-reported fatigue was evaluated as part of COU-AA-301, a randomized, placebo-controlled, phase III trial of abiraterone acetate and prednisone versus placebo and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel chemotherapy. This is the first phase III study in advanced prostate cancer to evaluate fatigue outcomes using a validated fatigue-specific instrument.Patients and methodsThe Brief Fatigue Inventory (BFI) questionnaire was used to measure patient-reported fatigue intensity and fatigue interference with activities of daily life. All analyses were conducted using prespecified responder definitions of clinically meaningful changes.ResultsA total of 797 patients were randomized to abiraterone acetate and prednisone, and 398 were randomized to placebo and prednisone. Compared with prednisone alone, in patients with clinically significant fatigue at baseline, abiraterone acetate and prednisone significantly increased the proportion of patients reporting improvement in fatigue intensity (58.1% versus 40.3%, P = 0.0001), improved fatigue interference (55.0% versus 38.0%, P = 0.0075), and accelerated improvement in fatigue intensity (median 59 days versus 194 days, P = 0.0155).Conclusions
In patients with mCRPC progressing after docetaxel chemotherapy, abiraterone acetate and prednisone yielded clinically meaningful improvements in patient-reported fatigue compared with prednisone alone.

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    • "Other symptoms of mCRPC include anorexia, anxiety, constipation, diarrhea, sleep disturbance, mucositis, nausea, peripheral sensory neuropathy, rash, vomiting, and urinary symptoms [[3]]. Fatigue is another dominant PC symptom and the most common adverse event resulting from mCRPC treatment [[4]]. These disease symptoms and noted side effects of treatment can significantly affect health-related quality of life (HRQOL). "
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    ABSTRACT: Background Metastatic castration-resistant prostate cancer (mCRPC) and its treatment significantly affect health-related quality of life (HRQOL). Our objectives were to evaluate and compare patient-reported outcome (PRO) claims granted by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for 5 recently approved mCRPC treatments and to examine key characteristics, development, and measurement properties of the PRO measures supporting these claims against current regulatory standards.Methods Five products approved for treatment of mCRPC by the FDA and the EMA (2010¿2013) were examined: enzalutamide, abiraterone, sipuleucel-T, cabazitaxel, and radium Ra 223 dichloride. United States (US) drug approval packages and European Public Assessment Reports were reviewed. PRO claims in the US labels and European Summaries of Product Characteristics and supporting measures were identified. For PRO measures supporting claims, a targeted literature review was conducted to identify information on key characteristics and measurement properties; this information was compared against FDA PRO guidance criteria.ResultsNine PRO ¿claims¿ were granted across 4 of 5 products reviewed. The EMA granted more claims (7 claims¿4 for pain, 3 for HRQOL) than the FDA (2 claims, both for pain). The Brief Pain Inventory¿Short Form (BPI-SF) worst pain item supported most pain claims and was the only measure supporting US claims. EMA pain claims were supported by BPI-SF worst pain (n¿=¿2) and average pain (n¿=¿1) items and the McGill Pain Questionnaire Present Pain Intensity component (n¿=¿1). EMA HRQOL claims were supported by the Functional Assessment of Cancer Therapy¿Prostate Module (n¿=¿2) and the EuroQol 5 Dimensions with visual analogue scale (n¿=¿1). Pain and prostate cancer¿specific HRQOL measures supporting claims met US regulatory standards for construct validity, reliability, and responsiveness; these properties were strongest for the BPI-SF worst pain item. Only the BPI-SF worst pain item has documented content validity in mCRPC.ConclusionsPRO label claims were commonly granted across the mCRPC products reviewed. Among the measures reviewed, only the BPI-SF worst pain item supported US label claims. The BPI-SF worst pain item is recommended for pain assessment for the evaluation of new mCRPC treatments.
    Health and Quality of Life Outcomes 07/2014; 12(1):104. DOI:10.1186/s12955-014-0104-5 · 2.10 Impact Factor
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    • "In patients with clinically significant fatigue at baseline, abiraterone significantly increased the number of patients reporting an improvement in fatigue intensity (58.1% versus 40.3%; P=0.0001) as well as the time to fatigue palliation (median 59 days versus 194 days; P=0.0155).78 In patients with clinically significant pain at baseline, abiraterone significantly increased the number of patients reporting palliation of pain (45% versus 28.8%; P=0.0005), as well as faster palliation (median time to palliation 5.6 months versus 13.7 months; P=0.0018). "
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    ABSTRACT: Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC). Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR) and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an abiraterone withdrawal response are presented. Future directions in the use of abiraterone, including optimal dosing strategies, the role of abiraterone in earlier disease settings, including castration sensitive, biochemically recurrent, or localized disease, and the rationale for combinatorial treatment strategies of abiraterone with enzalutamide and other targeted agents are also discussed.
    Cancer Management and Research 01/2014; 6(1):39-51. DOI:10.2147/CMAR.S39318
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    • "Other treatments have demonstrated the ability to provide palliation of symptoms in comparison with prednisone. Abiraterone acetate showed improved fatigue and pain [18, 19], while enzalutamide showed improvements in quality of life [13]. Furthermore, results from a recent study investigating radium-223 chloride versus placebo [20] have shown that treatment with radium-223 chloride prolongs the time to the first skeletal-related events, known to contribute to tumour-related pain [21]. "
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    ABSTRACT: BACKGROUND: Cabazitaxel significantly improves overall survival (OS) versus mitoxantrone in patients with metastatic castration-resistant prostate cancer after docetaxel failure. We examined patient survival at 2 years and tumour-related pain with cabazitaxel versus mitoxantrone. METHODS: Updated TROPIC data (cut-off 10 March 2010) were used to compare 2-year survival between treatment groups and assess patient demographics and disease characteristics. Factors prognostic for survival ≥2 years were assessed. Pain and Eastern Cooperative Oncology Group performance status were evaluated in the overall patient population. RESULTS: Median follow-up was 25.5 months. After 2 years, more patients remained alive following cabazitaxel than mitoxantrone [odds ratio 2.11; 95% confidence interval (CI) 1.33-3.33]. Treatment with cabazitaxel was prognostic for survival ≥2 years. Demographics/baseline characteristics were balanced between treatment arms irrespective of survival. Pain at baseline and pain response were comparable between treatment groups. Average daily pain performance index was lower for cabazitaxel versus mitoxantrone (all cycles; 95% CI -0.27 to -0.01; P = 0.035) and analgesic scores were similar. Grade ≥3 peripheral neuropathies were uncommon and comparable between treatment groups. CONCLUSIONS: Cabazitaxel prolongs OS at 2 years versus mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone.The study was registered with www.ClinicalTrials.gov (NCT00417079).
    Annals of Oncology 05/2013; 24(9). DOI:10.1093/annonc/mdt194 · 6.58 Impact Factor
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