M A Climent

Instituto Valenciano de Oncologia, Valenza, Valencia, Spain

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Publications (33)149.88 Total impact

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    ABSTRACT: Androgen deprivation treatment is the current standard first-line treatment for metastatic prostate cancer. For several years, docetaxel was the only treatment with a proven survival benefit for castration-resistant prostate cancer (CRPC). Since docetaxel became standard of care for men with symptomatic metastatic castration-resistant prostate cancer (CRPC), three treatment virtual spaces, for treatment and drug development in CPRC, have emerged: pre-docetaxel, docetaxel combinations and post-docetaxel. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 have been approved in the pre- or post-docetaxel setting in metastatic CRPC during the last few years. Patients are now living longer and experiencing better quality of life. Strategies for patient selection and treatment sequencing are therefore urgently required.
    Clinical and Translational Oncology 10/2014; 16(12). DOI:10.1007/s12094-014-1225-3 · 1.60 Impact Factor
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    ABSTRACT: Background: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). Methods: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (β-CTX) were analysed. Results: Patients with RCC who died or progressed had higher baseline β-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline β-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that β-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. Conclusion: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.
    British Journal of Cancer 06/2013; 109(1):121-130. DOI:10.1038/bjc.2013.272 · 4.82 Impact Factor
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    ABSTRACT: Previous studies suggest that expression of hypoxia markers may be associated with response to antiangiogenic drugs. Thus, we aimed to identify predictors of sunitinib outcome in clear-cell renal cell carcinoma (ccRCC). The expression of eight key proteins related to hypoxia (CAIX, HIF1A, HIF2A, VEGFA, VEGFR1, VEGFR2, VEGFR3 and PDGFRB) and P-glycoprotein were assessed by immunohistochemistry in 67 primary ccRCC samples from prospectively recruited patients treated with first-line sunitinib. The proteins expression, VHL inactivation and EGLN3 mRNA content were compared with the patients' response to sunitinib. High expression of HIF2A and PDGFRB was associated with better sunitinib RECIST objective response (P = 0.024 and P = 0.026; respectively) and increased VEGFR3 expression was associated with longer progression-free survival (P = 0.012). VEGFR3 overexpression showed a negative correlation with VEGFR3 polymorphism rs307826 (P = 0.002), a sunitinib resistance predictor. With respect to overall survival (OS), high VEGFA was associated with short (P = 0.009) and HIF2A with long (P = 0.048) survival times. High EGLN3 mRNA content was associated with shorter OS (P = 0.023). We found an association between several proteins involved in hypoxia and sunitinib efficacy. In addition, low VEGFR3 expression was associated with worse outcome and with VEGFR3 rs307826 variant allele, reinforcing VEGFR3 as a marker of sunitinib resistance.
    Annals of Oncology 06/2013; 24(9). DOI:10.1093/annonc/mdt219 · 6.58 Impact Factor
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    ABSTRACT: Bone metastases are a common complication of advanced prostate cancer and while they are less common in non-prostate genitourinary (GU) malignances, they have been reported in up to 35 % of patients with advanced renal cell carcinoma and bladder cancer. Furthermore, they may occur in more than two-thirds of those patients with bladder cancer who develop distant metastases. In the absence of bone-targeted therapies, approximately 50 % of all patients with metastatic bone disease from GU cancers experience at least one skeletal-related event within their lifetime. Zoledronic acid is a bisphosphonate that has been shown to delay or prevent the development of skeletal complications in patients with bone metastases and reduce bone pain in these patients. Furthermore, zoledronic acid has also demonstrated the ability to prevent osteopenia, which may occur with the prolonged use of some pharmacological interventions in patients with cancer.
    Clinical and Translational Oncology 04/2013; DOI:10.1007/s12094-013-1033-1 · 1.60 Impact Factor
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    ABSTRACT: Context: Controversies and uncertainties among integral management of advanced castration resistant prostate cancer continue to exist despite the number of evidence based clinical practice guidelines published with high international consensus. Objective: To develop a document that reviews the management of controversies in advanced castration resistant prostate cancer, with recommendations from the definition, to the management in hormonal maneuvers, first-line treatment and second-line with new treatments as cabazitaxel or abirarerone and the multidisciplinary approach of the pathology with the goal of finding the most efficient, best time to act and safety. Evidence Acquisition: Two meetings of a multidisciplinary group of experts involved in the management of this disease (Oncologist and Urologist) where pooled analysis of original literature and reached consensus document of recommendations on castration resistant prostate cancer, reviewing and attempting to address the current controversies of the disease. Evidence Synthesis: This document is endorsed by the corresponding Scientific Associations and Working Groups involved in the current management of Genitourinary Tumours: the Spanish Association of Urology (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary Group (SOGUG). Conclusions: With the adaptation and implementation of this Document of Recommendations for clinical practice are available for the first time, a real road map for quality, efficiency and safety in the management of patients with CRPC. (c) 2012 AEU. Published by Elsevier Espana, S.L. All rights reserved.
    Actas urologicas españolas 12/2012; 36(10):569–577. DOI:10.1016/j.acuroe.2012.06.001 · 1.15 Impact Factor
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    ABSTRACT: ContextControversies and uncertainties among integral management of advanced castration resistant prostate cancer continue to exist despite the number of evidence based clinical practice guidelines published with high international consensus.Objective To develop a document that reviews the management of controversies in advanced castration resistant prostate cancer, with recommendations from the definition, to the management in hormonal maneuvers, first-line treatment and second-line with new treatments as cabazitaxel or abirarerone and the multidisciplinary approach of the pathology with the goal of finding the most efficient, best time to act and safety.Evidence AcquisitionTwo meetings of a multidisciplinary group of experts involved in the management of this disease (Oncologist and Urologist) where pooled analysis of original literature and reached consensus document of recommendations on castration resistant prostate cancer, reviewing and attempting to address the current controversies of the disease.Evidence SynthesisThis document is endorsed by the corresponding Scientific Associations and Working Groups involved in the current management of Genitourinary Tumours: the Spanish Association of Urology (AEU) with the Uro-Oncoloy Group (GUO) and the Spanish Oncology of Genitourinary Group (SOGUG).Conclusions With the adaptation and implementation of this Document of Recommendations for clinical practice are available for the first time, a real road map for quality, efficiency and safety in the management of patients with CRPC.
    Actas urologicas españolas 11/2012; 36(10):569–577. DOI:10.1016/j.acuro.2012.06.004 · 1.15 Impact Factor
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    ABSTRACT: Background Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown.Patients and methodsWe carried out a prospective study to assess ovarian function in estrogen receptor (ER)-positive BC patients on tamoxifen who had at least 2 years of chemotherapy-induced amenorrhea (CIA) and postmenopausal E2 levels. Patients switched to exemestane and underwent a series of investigations including vaginal ultrasound, antimullerian hormone, follicle stimulating hormone (FSH), and E2. E2 measurements were made using a clinical assay (direct) and a highly sensitive (indirect) immunoassay for comparison.ResultsBoth E2 assays (indirect versus direct) showed a similar incidence of OFR 32% (95% CI 19.5-44.5) versus 30% (95% CI 17.7-42.3) and median time to OFR 5.4 months (95% CI 1.2-9.6) versus 6.0 months (95% CI 4.8-7.1).On multivariate analysis, the mean age at the start of exemestane treatment was the only marker associated with probability of OFR (OR: 0.44, 0.24-0.78; P = 0.006). According to a receiver operating characteristic (ROC) analysis, age <48 years predicted for OFR (sensitivity: 59%; 1-specificity: 17%; AUC: 0.796; P = 0.001). Patients with OFR had higher mean E2 levels (43.6 versus 5.76 pmol/l; P = 0.001) and a reduced disease-free survival [DFS; HR 9.3 (95% CI 3.3-48.0; P = 0.04)] than those without it.Conclusion Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.
    Annals of Oncology 10/2012; 24(3). DOI:10.1093/annonc/mds464 · 6.58 Impact Factor
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    ABSTRACT: Hormonal therapy allows effective control of cancer-related symptoms in advanced stages. However, the disease will progress in almost all these metastatic prostate cancer patient until becoming resistant to androgen suppression. The emergence of new drugs will most probably have open up new expectations regarding the treatment of this cancer. The aim of the present review has been to provide an overview of the current status of castration-resistant prostate cancer and to share the high expectations created with the new treatments. Evidence was obtained from multidisciplinary meetings with the participation of urologists and oncologists, where they pooled the analysis of original articles in the literature and defined the content of the article. Chemotherapy with docetaxel was a turning point in castration-resistant prostate cancer after the failure of hormonal therapy failure. For the first time, it achieved increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line choice treatment. Once the cancer has progressed, there is no clear alternative, although some novel agents have created expectations for the treatment of this type of cancer. The range of therapeutic options for castration-resistant prostate cancer has increased dramatically with the arrival of new drugs. At present, cabazitaxel, and in the near future, abiraterone, have been found to be effective drugs in second-line treatment after progression to docetaxel, increasing survival by 2-4 months and reducing risk of death by 30-35%.
    Actas urologicas españolas 12/2011; 36(6):367-74. DOI:10.1016/j.acuro.2011.10.010 · 1.15 Impact Factor
  • EJC Supplements 03/2010; 8(3):68-69. DOI:10.1016/S1359-6349(10)70066-5 · 9.39 Impact Factor
  • EJC Supplements 03/2010; 8(3):65-65. DOI:10.1016/S1359-6349(10)70056-2 · 9.39 Impact Factor
  • Cancer Research 02/2009; 69(2 Supplement):5022-0. DOI:10.1158/0008-5472.SABCS-5022 · 9.28 Impact Factor
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    ABSTRACT: Sorafenib improves progression-free survival in advanced clear-cell renal-cell carcinoma patients progressing to first-line therapy, as has been shown in the placebo-controlled international TARGET trial. The aim of this study is to report the results of the patients included in the Spanish centres in this trial. The records of the patients in the database of the TARGET trial have been reviewed. Data about progression-free survival, overall survival and toxicity have been collected in order to do this subpopulation analysis. A total of 15 patients have been included (sorafenib arm 7, placebo arm 8). A trend to an improved progression-free survival in the sorafenib arm has been observed period Toxicity in the sorafenib arm has been manageable. The analysis of these 15 patients has shown efficacy and toxicity results that follow the trend observed for the overall international population.
    Clinical and Translational Oncology 11/2007; 9(10):671-3. DOI:10.1007/s12094-007-0120-6 · 1.60 Impact Factor
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    ABSTRACT: Up to 50% of patients with bladder cancer cannot be treated with cisplatin because they are considered unfit due to poor renal function. Gemcitabine and oxaliplatin are active, nonnephrotoxic therapies with nonoverlapping toxicity profiles that provide an alternative therapy for this group of patients. In a multicenter study, patients received gemcitabine 1200 mg/m(2) on days 1 and 8 and oxaliplatin 100 mg/m(2) on day 8 every 21 days. Eligible criteria were creatinine clearance >30 ml/min and/or Eastern Cooperative Oncology Group (ECOG) performance status of two or less. Forty-six patients were assessable for response and toxicity. Median age was 69 years (range 52-85), median ECOG two (range 0-2). Median number of metastatic sites was 2 (range 1-6). Median creatinine clearance was 50.73 ml/min (range 30-87). A total of 187 cycles were given with a median of 5 (range 1-6). Hematological toxicity was mild with grade 3-4 peripherical neuropathy occurring in 4% of patients. Overall response rate was 48% (three complete response, 19 partial response, seven stable disease and 17 progressive disease). Median time to disease progression was 5 months. Gemcitabine-oxaliplatin is an active and tolerable combination with response rate that merits further study in patients with impaired renal function but good performance status.
    Annals of Oncology 08/2007; 18(8):1359-62. DOI:10.1093/annonc/mdm160 · 6.58 Impact Factor
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    Breast Cancer Research 01/2005; 7:1-1. DOI:10.1186/bcr1228 · 5.33 Impact Factor
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    ABSTRACT: A phase II randomised trial was conducted to evaluate the tolerability and activity of weekly or 3-weekly docetaxel in patients with metastatic breast cancer. Eighty-three patients with histologically proven metastatic breast cancer were randomised to receive either docetaxel 40 mg/m2 weekly for 6 consecutive weeks followed by 2 weeks without treatment (n = 41), or docetaxel 100 mg/m2 on day 1 every 3 weeks (n = 42). The incidence of all grade 3-4 adverse events was higher in the 3-weekly group than in the weekly group (96 versus 44), and the number of patients with grade 3-4 adverse events was also greater in the 3-weekly group (31 versus 20). Analysis of individual adverse events tended to favour the weekly regimen. Intent-to-treat overall response rate was 34% and 33% in the weekly and 3-weekly groups, respectively. Median time to progression was 5.7 and 5.3 months after weekly and 3-weekly docetaxel, respectively, and median time to treatment failure was 4.1 and 4.9 months, respectively. Weekly docetaxel is an active regimen in metastatic breast cancer with comparable efficacy to 3 weekly docetaxel. Although both schedules were well tolerated, weekly docetaxel appears to have a more favourable toxicity profile.
    Annals of Oncology 10/2004; 15(9):1358-65. DOI:10.1093/annonc/mdh349 · 6.58 Impact Factor
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    ABSTRACT: To select a group of useful serum markers in renal cell carcinoma (RCC) with investigational purpose in future. Periodic determination in serum of 21 RCC patients of the following markers: EGR, RPC, hemogram and leucocyte differential count (LDC), standard biochemist parameters, beta-2 microglobuline, CEA, CA 12.5, CA 50, CA 15.3, ferritin, interleukin-6, serum interleukin-2 receptor, TNF-alpha and TPSA. Different elements within the LDC had relations with the presence of symptoms/signs, tumour size, pathological stage and disease progression. There was a significant increase of beta-2 microglobuline and sIL-2 receptor when disease progressed, as well as a similar statistical trend with RPC and alkaline phosphatases. Beta-2 microglobuline and sIL-2 receptor also decreased after treatment of the disease progression. We will keep analysing hemogram, LDC and standard byochemics, RPC, ferritin, beta-2 microglobuline and sIL-2 receptor only with investigational purposes, obviating the determination of the rest of the tested markers.
    Actas urologicas españolas 06/2004; 28(5):381-6. · 1.15 Impact Factor
  • EJC Supplements 03/2004; 2(3):132-132. DOI:10.1016/S1359-6349(04)90865-8 · 9.39 Impact Factor
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    ABSTRACT: Objectives To select a group of useful serum markers in renal cell carcinoma (RCC) with investigational purpose in future.Material And Methods Periodic determination in serum of 21 RCC patients of the following markers: EGR, RPC, hemogram and leucocyte differential count (LDC), standard biochemist parameters, ß-2 microglobuline, CEA, CA 12.5, CA 50, CA 15.3, ferritin, interleukin-6, serum interleukin-2 receptor, TNF-α and TPSA.ResultsDifferent elements within the LDC had relations with the presence of symptoms/signs, tumour size, pathological stage and disease progression. There was a significant increase of ß-2 microglobuline and sIL-2 receptor when disease progressed, as well as a similar statistical trend with RPC and alkaline phosphatases. ß-2 microglobuline and sIL-2 receptor also decreased after treatment of the disease progression.Conclusions We will keep analysing hemogram, LDC and standard byochemics, RPC, ferritin, ß-2 microglobuline and sIL-2 receptor only with investigational purposes, obviating the determination of the rest of the tested markers.
    Actas urologicas españolas 01/2004; 28(5). DOI:10.4321/S0210-48062004000500007 · 1.15 Impact Factor
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    ABSTRACT: To describe the clinical characteristics and treatment results obtained with the application of a homogeneous treatment protocol in 1490 patients with germ-cell tumours (GCT) registered in the 55 hospitals belonging to the Spanish Germ-Cell Cancer Group (GG) during the period between January 1994 and April 2001. In general, surveillance was the common policy for stage I patients without local poor prognosis factors, whereas they received adjuvant chemotherapy in case those factor were present. Chemotherapy schedules used in advanced cases were cisplatin and etoposide (EP) for seminoma and BEP or BOMP-EPI in non-seminoma, according to whether the patient was in the good or poor prognosis IGCCCG (International Germ-Cell Cancer Collaborative Group) group. Excision of residual masses was mandatory in non-seminomatous germ-cell tumour (NSGCT). Initial local symptomatology was increased testis size in 90% of cases. Sonography was an excellent diagnostic tool to suggest tumour. Non-seminoma (64.2%) was more frequent than seminoma (35.8%). Approximately 10% had the antecedent of cryptorchidism. Non-seminoma patients were 7 years younger than seminoma. Right testis was involved predominantly. Pre-orchidectomy tumour markers were elevated in 21% of seminoma (betaHGC) and 79% in non-seminoma (alphaFP and/or betaHGC). Scrotum violation occurred in only 1.8%. There were significant differences among stage I and the IGCCCG prognosis groups related to a longer interval between the first symptom and orchiectomy. Eighteen percent of non-seminomatous germ-cell tumour belonged to the poor prognosis IGCCCG group. With a median follow-up to 33 months, this series has achieved a 3 year overall survival of 98% for seminoma and 94% for non-seminoma. Only 10% of excised residual masses present after chemotherapy contained malignant cells. Spanish GCT have a similar clinical pattern to that described in the other occidental countries except for a slight increased proportion of non-seminoma upon seminoma. Co-operative groups as GG are unique structures to obtain quick and wide experience on the treatment of testis tumours, contributing to achieve a high cure rate.
    European Urology 01/2003; 42(6):553-62; discussion 562-3. DOI:10.1016/S0302-2838(02)00439-6 · 12.48 Impact Factor
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    ABSTRACT: d y G. Zanón l
    Clinical and Translational Oncology 03/2002; 4(3):154-156. DOI:10.1007/BF02732345 · 1.60 Impact Factor

Publication Stats

435 Citations
149.88 Total Impact Points

Institutions

  • 1998–2013
    • Instituto Valenciano de Oncologia
      Valenza, Valencia, Spain
  • 2012
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2003
    • Institut Català d'Oncologia
      Barcino, Catalonia, Spain
  • 1995
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 1992
    • Hospital de la Santa Creu i Sant Pau
      Barcino, Catalonia, Spain