K Fizazi

Institut de Cancérologie Gustave Roussy, Villejuif, Île-de-France, France

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Publications (164)798.26 Total impact

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    ABSTRACT: The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.
    Annals of Oncology 01/2013; 24(5). DOI:10.1093/annonc/mds624 · 6.58 Impact Factor
  • EAU Guidelines 2013, Edited by EAU Guidelines Office, 01/2013: chapter 7: pages 1-48; European Association of Urology., ISBN: 978-90-79754-71-7
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    ABSTRACT: In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues.The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
    Annals of Oncology 11/2012; 24(4). DOI:10.1093/annonc/mds579 · 6.58 Impact Factor
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    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.
    Annals of Oncology 11/2012; 24(4). DOI:10.1093/annonc/mds585 · 6.58 Impact Factor
  • Progrès en Urologie 11/2012; 22(13):780. DOI:10.1016/j.purol.2012.08.094 · 0.77 Impact Factor
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    European Urology Supplements 11/2012; 11(5):188–189. DOI:10.1016/S1569-9056(13)60379-6 · 3.37 Impact Factor
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    ABSTRACT: Background An early serum tumor marker (TM) decline during chemotherapy was shown to independently predict survival in patients with poor-prognosis disseminated non-seminomatous germ-cell tumors (NSGCTs). The aim of this study was to assess whether a TM decline (TMD) also correlates with the outcome in the salvage setting.Patients and methodsData regarding 400 patients with progressive or relapsed disseminated NSGCTs after first-line chemotherapy prospectively accrued onto two phase III clinical trials were obtained. Serum alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (hCG) were assessed at baseline and after 6 weeks of chemotherapy. A total of 297 patients, 185 and 112 in the training and validation sets, with initially abnormal TMs for whom a change from baseline could be established were used for this analysis.ResultsAn unfavorable decline in either AFP or hCG was predictive of progression-free survival (PFS) [hazard ratio, HR = 2.15, (95% CI 1.48-3.11); P < 0.001; 2-year PFS rate: 50% versus 26%] as was the Lorch prognostic score (LPS). In the multivariate analysis, an unfavorable TMD, stratified based on the LPS, was an independent adverse prognostic factor for PFS and OS.Conclusion An unfavorable TMD during the first 6 weeks after chemotherapy is associated with a poorer outcome in patients with relapsed disseminated NSGCTs.
    Annals of Oncology 10/2012; 24(2). DOI:10.1093/annonc/mds504 · 6.58 Impact Factor
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    ABSTRACT: The treatment of renal cell carcinoma has dramatically changed in the past 6 years with the approval of seven new drugs since 2006. although treatment algorithms have been reported and updated every year since 2006, the choice of targeted therapy is not always easy. Selecting a targeted agent in metastatic renal cell carcinoma (mRCC) should take into account various parameters, including the status of the disease, the histology, the status of the patient and finally the availability of the drugs in each country. In addition, in front of every patient, the physician will need to raise important questions such as whether the patient should be treated, should receive surgery, and also what is his prognostic group. The different options are described in this manuscript.
    Annals of Oncology 09/2012; 23 Suppl 10:x309-x312. DOI:10.1093/annonc/mds352 · 6.58 Impact Factor
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    ABSTRACT: Clearly, no neoplasm other than prostate cancer has benefited from so many breakthroughs since the beginning of this decade: the past two years can be considered exceptional due to the number of emerging agents against castration-resistant prostate cancer (CRPC), which have demonstrated positive outcomes in phase III trials. Until 2010, docetaxel (Taxotere) was the only agent capable of improving survival in patients with metastatic CRPC. Since then, positive results from phase III trials have been reported for sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, while other promising agents including notably orteronel, ipilimumab and cabozantinib are currently under study. Taken together, the incorporation of these agents in the routine management of patients with CRPC is likely to expand their median life expectancy, which was only ∼1 year until the early 2000, to >30 months in the near future. The availability of these agents will lead to new challenges and questions, such as: Can our societies afford the costs? Should we use these agents sequentially or in combination with an incremental benefit? Can we personalise treatment based on the biology of the individual's disease? How will we develop new active compounds in the context where a half dozen approved agents may confound their potential overall survival effect?
    Annals of Oncology 09/2012; 23 Suppl 10:x264-x267. DOI:10.1093/annonc/mds353 · 6.58 Impact Factor
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    Cancer Research 06/2012; 72(8 Supplement):823-823. DOI:10.1158/1538-7445.AM2012-823 · 9.28 Impact Factor
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    ABSTRACT: Background Skeletal-related events (SREs) cause significant morbidity in patients with solid tumours and bone metastases (BMs). An ad hoc analysis was undertaken to compare the effect of denosumab with zoledronic acid (ZA) in the prevention of SREs in patients with BMs secondary to solid tumours who participated in the denosumab pivotal phase 3 studies. Methods Patients with breast cancer (N = 2046), prostate cancer (N = 1901), or other solid tumours (N = 1597) and BMs were randomly assigned in a 1:1 ratio to receive subcutaneous denosumab 120 mg or IV ZA 4 mg (adjusted for renal function) every 4 weeks. Patient-level data from three identically designed, double-blind, double-dummy studies were combined. Time to first on-study SRE and time to first and subsequent SREs were analysed using the Cox proportional hazards model and Anderson–Gill method, respectively. Findings Patients received denosumab (N = 2776) or ZA (N = 2768). Denosumab was superior to ZA in delaying time to first on-study SRE and time to first and subsequent SREs. Denosumab reduced the risk of a first SRE by 18% compared with ZA (HR 0.82 [95% confidence interval (CI): 0.75, 0.89], p < 0.0001), reflecting a delay in median time to first SRE of 8.2 months. Denosumab also reduced the risk of first and subsequent SREs by 19% (HR 0.81 [95% CI: 0.74, 0.88], p < 0.0001) compared with ZA. Disease progression and survival were similar between groups. Incidence of adverse events (96.2% of denosumab group and 96.7% of ZA group), serious adverse events (56.2% of denosumab group and 57.3% of ZA group), and osteonecrosis of the jaw (1.7% of denosumab and 1.3% of ZA; p = 0.18) were similar in both groups. Hypocalcaemia was more frequent with denosumab (9.5% versus 4.8% for ZA) and acute phase reactions (first 3 days) were more common with ZA (20.4% versus 8.7% for denosumab). Interpretation This integrated analysis confirmed results from the individual studies; denosumab was superior to ZA in reducing the risk of both first and multiple SREs among patients with solid tumours and BMs. Funding Amgen Inc. A.T. Stopeck is a consultant for Amgen and Novartis; G. Richardson has received honoraria and research funding from Amgen; S. Siena has no conflicts of interest to declare; A. Lipton is a member of the speakers’ bureau, is a consultant, has received research support from Amgen and Novartis, and has provided expert testimony for Novartis; J. Brown has received consultancy fees from Amgen and Novartis, and payment for lectures from Amgen, Novartis, and Bayer; K. Fizazi has participated in Advisory Boards for Amgen and Novartis; D. Henry is a member of the speakers’ bureau, has participated in research and advisory boards for Amgen and Johnson and Johnson; F. Saad is a consultant and has carried out research for Amgen and Novartis; C. Ke and A. Braun are employed by Amgen and own stock.
    European Journal of Cancer 04/2012; 48:S8. DOI:10.1016/j.ejca.2012.02.030 · 4.82 Impact Factor
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    ABSTRACT: To compare the overall survival rates of good-prognosis carcinomas of an unknown primary site (CUPS) patients treated with cisplatin alone (C) or in combination with gemcitabine (CG). Good prognosis was defined according to the GEFCAPI (Groupe d'Etude Français des Carcinomes de site Primitif Inconnu) classification by PS (Performance Status) ≤ 1 and LDH (Lactate Deshydrogenase) within the normal range. Patients were randomly assigned to receive C or CG. Patients in the C arm received cisplatin 100 mg/m(2) repeated every 3 weeks. In the CG arm, chemotherapy consisted of gemcitabine 1250 mg/m(2) on days 1 and 8 and cisplatin 100 mg/m(2) IV on day 1, repeated every 3 weeks. The original plan was to accrue 192 patients in order to detect a 20% difference in overall survival. Fifty-two patients were enrolled (arm A: 25; arm B: 27). The trial was stopped early due to insufficient accrual. The median overall survival (OS) rate was 11 months [95% confidence interval: 9-20] and 8 months [95%CI: 6-12], in the CG arm and in the C arm, respectively. The 1-year survival rate was 46% [95%CI: 28-64] in the combination arm and 35% [95%CI: 19-56] in the C arm (log rank test: p=0.73). The median progression-free survival (PFS) rate was 5 [95%CI: 3-11] and 3 [95%CI: 1-8] months in the CG and in the C arm, respectively. The 1-year PFS rate was 29% [95%CI: 15-48] in the combination arm and 15% [95%CI: 5-35] in the C arm (log rank test: p=0.27). No toxic deaths occurred. Grade 3-4 neutropenia (63% versus 12%) and grade 3-4 thrombocytopenia (37% versus 4%) were more frequent in the CG arm than in the C arm. A non-significantly better outcome was observed with CG as compared to C in patients with CUP and a non-unfavourable prognosis. The toxicity profile of the combined arm was represented by haematologic toxicity with thrombocytopenia and leuconeutropenia. International collaboration is required to conduct phase III trials in patients with CUP.
    European journal of cancer (Oxford, England: 1990) 02/2012; 48(5):721-7. DOI:10.1016/j.ejca.2012.01.011 · 4.82 Impact Factor
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    ABSTRACT: Bone metastases in prostate cancer treatment stand as a clinical challenge in order to maintain quality of life and prevent pain and skeletal-related events. Bone metastases predominantly disrupts the dynamic equilibrium existing in healthy bone between osteogenesis and osteolysis. Therefore, bone microenvironment targeting agents under development are emerging as a specific component of care in the treatment of patients with metastatic prostate cancer.
    Oncologie 02/2012; 14(2). DOI:10.1007/s10269-012-2121-5 · 0.08 Impact Factor
  • European Urology Supplements 02/2012; 11(1):e127-e127a. DOI:10.1016/S1569-9056(12)60126-2 · 3.37 Impact Factor
  • Y Loriot, C Massard, K Fizazi
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    ABSTRACT: Prostate cancer is the most common male cancer and one of the top causes of male cancer-related death. Most patients with prostate cancer respond to initial androgen deprivation therapy before progressing to castration-resistant prostate cancer (CRPC) and eventually developing bone metastases. Growth of prostate cancer metastases in the bone microenvironment produces numerous factors that disrupt the dynamic equilibrium of osteogenesis and osteolysis existing in healthy bone, leading to progressive morbidity, poor quality of life, and increased treatment costs. Materials and methods: Relevant studies of CRPC and targeted therapies were identified from literature and clinical trial databases, websites, and conference abstracts. Available data on agents potentially targeting bone metastatic CRPC or the bone microenvironment in patients with CRPC are discussed, including inhibitors of tumor growth/survival and bone turnover (SRC family kinase inhibitors, endothelin-1 inhibitors, MET inhibitors, and thalidomide and its derivatives), inhibitors of bone turnover (bisphosphonates and receptor activator of nuclear factor-kB ligand inhibitors), antiangiogenic agents (vascular endothelial growth factor receptor and platelet-derived growth factor blockers), prostate cancer vaccines, and bone-directed radiopharmaceuticals. With increasing data availability demonstrating tumor-bone microenvironment interactions and routine incorporation of bone-related end points into CRPC trials, bone microenvironment-targeted agents are likely to become an increasingly important component of CRPC treatment.
    Annals of Oncology 01/2012; 23(5):1085-94. DOI:10.1093/annonc/mdr573 · 6.58 Impact Factor
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    ABSTRACT: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. Although testicular cancer has excellent cure rates, the choice of treatment centre is of the utmost importance. Expert centres achieve better results for both early stage testicular cancer (lower relapse rates) and overall survival (higher stages within clinical trials). For patients with clinical stage I seminoma, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment.
    Actas urologicas españolas 12/2011; 36(3):127-45. DOI:10.1016/j.acuro.2011.06.017 · 1.15 Impact Factor
  • Cahiers de Nutrition et de Diététique 12/2011; 46:S47. DOI:10.1016/S0007-9960(11)70076-1
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    ABSTRACT: This open-label phase II trial assessed mitoxantrone/prednisone (M/P) with and without siltuximab (CNTO 328), an anti-interleukin-6 chimeric monoclonal antibody, for patients with metastatic castration-resistant prostate cancer who received prior docetaxel-based chemotherapy. Part 1 assessed the safety of biweekly siltuximab 6 mg/kg plus M 12 mg/m(2) every 3 weeks and P. Part 2 assessed efficacy and safety of siltuximab plus M/P versus M/P alone. The primary end-point was progression-free survival (PFS). Progression was defined as progressive disease per Response Evaluation Criteria in Solid Tumours (RECIST), or ≥ 3 new skeletal lesions with clinical deterioration or without deterioration confirmed by repeated bone scan. Rising prostate-specific antigen was not considered progression. Siltuximab plus M/P was well tolerated in Part 1 (n=9). In Part 2, 48 and 49 patients received siltuximab plus M/P or M/P alone, respectively. Enrolment was prematurely terminated by the Independent Data Monitoring Committee since an apparent imbalance in patient baseline characteristics (favoring the M/P only arm) made it unlikely that the study could achieve its primary efficacy end-point. Median PFS was 97 days with siltuximab combination and 228 days with M/P alone (hazard ratio, 1.72; P=0.043). Use of a novel non-validated PFS definition may have contributed to this result. Abnormal laboratory assessments were more frequent with the combination. Infection and febrile neutropenia rates were similar between groups. Greater C-reactive protein suppression was achieved during siltuximab combination treatment compared with M/P alone (P=0.0003). While siltuximab plus M/P appeared well tolerated, improvement in outcomes was not demonstrated.
    European journal of cancer (Oxford, England: 1990) 11/2011; 48(1):85-93. DOI:10.1016/j.ejca.2011.10.014 · 4.82 Impact Factor
  • Value in Health 11/2011; 14(7). DOI:10.1016/j.jval.2011.08.1229 · 2.89 Impact Factor

Publication Stats

3k Citations
798.26 Total Impact Points

Institutions

  • 1994–2014
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France
  • 2013
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
  • 2010–2012
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2007
    • Institut du Cancer de Montpellier Val d'Aurelle
      Montpelhièr, Languedoc-Roussillon, France
  • 2004
    • Martin Luther University Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2002–2004
    • University of Houston
      Houston, Texas, United States
    • University of Texas MD Anderson Cancer Center
      • Genitourinary Medical Oncology
      Houston, Texas, United States
  • 2001
    • Centre Léon Bérard
      Lyons, Rhône-Alpes, France
  • 1998
    • Hôpital d'instruction des armées du Val-de-Grâce
      Lutetia Parisorum, Île-de-France, France