Pere Gascón

Hospital Clínic de Barcelona, Barcino, Catalonia, Spain

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Publications (149)631.17 Total impact

  • Pere Gascon
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    ABSTRACT: The loss of patents covering many biopharmaceutical/biological agents in the mid 1990s led to the introduction of a new generation of drugs: biosimilars. These new agents, produced by living cells just as the originator drugs, are chemically highly similar to endogenous human proteins; characterized by three-dimensionally complex, high molecular weight compounds. Among the first biosimilars used in haematology-oncology were erythropoietin and granulocyte colony-stimulating factor. After five years of use in clinical practice, the efficacy and safety profile of biosimilars approved by the European Medicines Agency is excellent. Over the next year or two, biosimilar monoclonal antibodies (MoAbs) will become available; the first will be rituximab and trastuzumab. Not only are MoAbs more complex in terms of molecular weight and number of amino acids than the first biosimilars, but they are also anticancer drugs, not merely supportive treatments like their predecessors. This opens up important questions. How are regulatory agencies to assess their clinical efficacy, immunogenicity and safety? Is the neoadjuvant clinical setting the best to evaluate them? What will regulatory agencies decide in terms of switching an originator molecule for a biosimilar or extrapolating efficacy results from one pathology to another? Once biosimilars of rituximab and trastuzumab are approved, several challenging issues will need to be addressed such as how to maintain appropriate pharmacovigilance, how to extrapolate across indications, and issues concerning automatic substitution. There is currently no consensus in any of these areas. This review addresses all these issues: new challenges that the oncology community will face in the near future.
    No preview · Article · Dec 2015
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    ABSTRACT: The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio®). MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio®. Data were analyzed using both the patient and cycle as unit of analysis. Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients. The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice.
    Full-text · Article · Aug 2015 · Supportive Care Cancer

  • No preview · Article · Aug 2015 · Cancer Research
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    ABSTRACT: This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.
    Full-text · Article · Jun 2015 · Supportive Care Cancer

  • No preview · Article · May 2015 · Cancer Research
  • P Gascon
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    ABSTRACT: The New Year has brought a renovated editorial team to the Journal of Clinical and Translational Oncology.At the end of last year the Steering Committee of FESEO has appointed me as new Editor-in-Chief of the Journal, the successor to Dr. Andrés Cervantes and Dr. Rosario Perona to whom heartfelt thanks are due for their precious work.I am honoured to take the leadership of the Journal, which is a great challenge and a big responsibility.I have been following CTO for the last years and I can say that the Journal we have now inherited is a much better one that the one I recall many years ago.Overall, 2014 has been a successful year, papers submissions have been over 1,000 and the rejection rate worked up to 80 %. Another noteworthy feature of 2014 was the continuing improvement in publication times while maintaining high standards which lead a significant increase of citations that have continuously growing.From the pages of this Journal, I want to thank the past Editors, thanks to their ...
    No preview · Article · Jan 2015 · Clinical and Translational Oncology
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    ABSTRACT: Unlabelled: The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal- or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by β1 integrin mechano-sensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in β1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), β1 expression, and ERK1/2 (pT202/Y204) than ADC-TAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (>50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or β1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs. Implications: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.
    No preview · Article · Oct 2014 · Molecular Cancer Research
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    ABSTRACT: Niemann-Pick disease type C (NPC) is a lipid storage disorder mainly caused by mutations in the NPC1 gene. Approximately 60% of these mutations are missense changes that may induce reduced NPC1 protein levels by increased degradation via ubiquitin-proteasome. This is the case for the most prevalent worldwide mutation, p.Ile1061Thr, and also for other three missense changes. In this study, we analysed the NPC1 levels in fibroblasts from eighteen NPC patients presenting missense mutations. We found that fourteen of these cells lines showed decreased levels of NPC1. Six of these cell lines were homozygous whereas the other eight were associated with a frame shifting mutation. We focused our attention in the NPC homozygous samples and we demonstrated that in most of the cases NPC1 reduction was a consequence of a decrease of its half-life. NPC cells were treated with the proteasome inhibitors MG132 or ALLN, both widely used as a research tools, but also with bortezomib, the first proteasome inhibitor to reach clinical applications, but never used in NPC disease. We observed that after treatment the mutant NPC1 protein levels were partially recovered in most of the cell lines. Importantly, these mutant proteins partially recovered their activity and substantially reduced free cholesterol levels. These results suggest that enhancing the NPC1 protein stability by using proteasome inhibitors, their functionality might be recovered and this might represent a therapeutical approach for future treatments of NPC disease caused by specific missense mutations. This article is protected by copyright. All rights reserved.
    Full-text · Article · Aug 2014 · FEBS Journal

  • No preview · Article · Jul 2014 · European Journal of Cancer

  • No preview · Article · Jul 2014 · European Journal of Cancer

  • No preview · Article · Jul 2014

  • No preview · Article · Jul 2014 · European Journal of Cancer
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    ABSTRACT: The mechanisms underlying the abundance of tumor associated fibrobasts (TAFs) in non-small cell lung cancer (NSCLC) remain poorly understood. To address this gap of knowedge, we examined the relative contribution of mechanical (i.e. matrix rigidity) and soluble biochemical (i.e. serum) cues in the accumulation of primary TAFs from either adenocarcinoma (ADC) or squamous cell carcinoma (SQC) NSCLC patients. For this purpose, fibroblasts were cultured on collagen-I coated gels engineered to exhibit either normal- or tumor-like stiffnesses at different serum concentrations. In fibroblasts from non-malignant tissue, matrix stiffening alone was sufficient to increase fibroblast accumulation by 20%. In addition, matrix stiffening-induced accumulation was dominant or comparable to that due to soluble growth factors up to moderate serum concentrations. These mechanical stimulatory effects were β1 integrin-dependent, and were associated with both increased integrin mechanosensing through FAKpY397and a post-transcriptionally-driven rise in β1 integrin expression. The latter mechanoregulatory circuit could be extended to TAFs in a subtype-dependent fashion, since SQC-TAFs exhibited higher FAKpY397 and β1 expression than ADC-TAFs. Remarkably, SQC-TAF density was enhanced > 50% in response to matrix stiffening, whereas they were largely desensitized to serum. Conversely, substantial accumulation of ADC-TAFs required large serum concentration, whereas it was poorly induced by either matrix stiffening or low serum concentration. These results reveal that a therapeutic strategy aiming to inhibit soluble growth factors may be effective against ADC-TAFs, whereas a strategy aiming to rescue normal lung elasticity may be more efficient against SQC-TAFs.
    No preview · Conference Paper · Apr 2014
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    ABSTRACT: Molecular characterization of radical prostatectomy specimens after systemic therapy may identify a gene expression profile for resistance to therapy. This study assessed tumor cells from patients with prostate cancer (PC) participating in a phase-II neoadjuvant docetaxel (D) and androgen deprivation (AD) trial to identify mediators of resistance. Transcriptional level of 93 genes from a D-resistant PC cell lines microarray study was analyzed by Taqman low-density arrays in tumors from patients with high-risk localized PC (36 surgically treated, 28 with neoadjuvant D+AD). Gene expression was compared between groups and correlated with clinical outcome. VIM, AR and P65 were validated by immunohistochemistry. CD44 and ZEB1 expression was tested by immunofluorescence in cells and tumor samples. Parental and D-resistant CRPC cell lines were tested for epithelial-to-mesenchymal transition (EMT) markers before and after D-exposure. Reversion of EMT phenotype was investigated as a D-resistance reversion strategy. Expression of 63 (67.7%) genes differed between groups (P<0.05), including genes related to androgen receptor, NFKB transcription factor, and EMT. Increased EMT markers expression correlated with radiological relapse. D-resistant cells had increased EMT and stem-like cell markers expression. ZEB1 siRNA transfection reverted D-resistance and reduced CD44 expression in DU-145R and PC-3R. Before D-exposure, a selected CD44+ subpopulation of PC-3 cells exhibited EMT phenotype and intrinsic D-resistance; ZEB1/CD44+ subpopulations were found in tumor cell lines and primary tumors; this correlated with aggressive clinical behavior. This study identifies genes potentially related to chemotherapy resistance and supports evidence of the EMT role in docetaxel resistance and adverse clinical behavior in early PC.
    Full-text · Article · Mar 2014 · Molecular Cancer Therapeutics
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    ABSTRACT: The purpose of this prospective cohort study was to assess the feasibility of outpatient treatment in patients with cancer and objectively confirmed pulmonary embolism (PE), and to compare the performance of the different prognostic scales available in this setting. Patients were selected for outpatient management according to a set of exclusion criteria. Outcomes at 30 and 90 days of follow-up included thromboembolic recurrences, major bleeding, and all-cause death. The performance of 4 prognostic scales (Pulmonary Embolism Severity Index, Geneva Prognostic Score, POMPE-C, and Registro Informatizado de Enfermedad Tromboembólica [RIETE registry]) was evaluated. Of 138 patients, 62 (45%) were managed as outpatients. Incidental PE constituted 47% of the sample. Most patients treated at home had an incidentally detected PE (89%). The rate of recurrence and major bleeding events was similar in both groups. Mortality rates were higher for patients admitted to the hospital compared with outpatients at 30 days (18% vs 3%; P=.06) and 90 days (34% vs 10%; P=.001) of follow-up. None of the patients selected for home treatment required further admission because of PE complications. None of the prognostic models developed for symptomatic PE was significantly associated with 30-day mortality. Improved survival outcomes were observed in incidentally detected PEs compared with acute symptomatic events (overall mortality rates, 3.2% vs 18.4%; P=.006). A large proportion of patients with cancer and PE may be safely treated as outpatients, especially those with incidental PE. Cancer-specific prognostic scales including incidental PE should be developed for the optimal management of PE in this setting.
    No preview · Article · Mar 2014 · Journal of the National Comprehensive Cancer Network: JNCCN

  • No preview · Article · Jan 2014 · Molecular Cancer Therapeutics
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    ABSTRACT: The objective of the present study was to describe the prevalence and management of anaemia and iron deficiency (ID) in treatment-naïve patients with solid tumours in Spain and the incidence of anaemia over 4 months of cancer treatment in clinical practice. Multicentre, prospective and observational study in newly diagnosed cancer patients. Data on anaemia and iron parameters and its management were collected prior to the initiation of chemotherapy, at each cycle of chemotherapy and after 4 months of treatment. The main outcomes of the study were the prevalence of anaemia at baseline, its incidence during cancer treatment and the prevalence of absolute ID (AID) and functional ID (FID) prior to chemotherapy initiation. A total of 295 patients were included in the study. Anaemia was present at diagnosis in 38.6 % of patients and was treated only in 32.5 % of those. A total of 106 patients (60.2 %) without anaemia at baseline developed anaemia during cancer treatment. Serum ferritin and transferrin saturation data were available for 151 of the patients (51.2 %) included in the study. The overall prevalence of ID was 59 %: 48 patients (31.8 %) presented with AID and 41 patients (27.2 %) presented with FID before starting anti-cancer therapy. Thirty-three of 44 non-anaemic iron-deficient patients did not receive any type of iron supplementation before initiating cancer therapy. Iron parameters are not commonly measured in newly diagnosed cancer patients. A correct evaluation and early management of ID could reduce the incidence of treatment-related anaemia in cancer patients.
    No preview · Article · Jan 2014 · Clinical and Translational Oncology
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    ABSTRACT: Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.
    Full-text · Article · Jan 2014 · Cell Reports
  • Laura Visa · Cristina Nadal · Pere Gascon
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    ABSTRACT: The Hedgehog (Hh) signalling pathway plays an important role in the formation and maintenance of cancer stem cell (CSC) and in the acquisition of epithelial-mesenchymal transition (EMT). Since these two properties are very relevant in cancer biology: cell invasion, metastasis, drug resistance and, the appearance of cancer relapse, the Hh pathway is considered an important target for future cancer treatments. Over the last few years, several small-molecules inhibitors have been designed and introduced in cancer clinical trials with some of them showing already very promising results. Currently, many of such inhibitors are in clinical development being tested in ongoing clinical trials. In addition, many products of the so called nutraceutical family (curcumin, soy isoflavones, vitamin D, resveratrol and epigallocatechin-3 gallate) have been shown to inhibit tumor growth through downregulation of the Hh signaling pathway. The inhibition of the Hh signalling pathway should led to the suppression of cancer cell growth, invasiveness, metastasis and eventually prevent tumor recurrences. The future design of novel strategies combining inhibitors of the Hh pathway with nutraceuticals and inhibitors of other signaling pathways to regulate activated Hedgehog could bring new tools for cancer treatment. © 2014 Springer Science+Business Media Dordrecht. All rights reserved.
    No preview · Chapter · Jan 2014
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    ABSTRACT: Demographic, personal, clinical, and behavioral factors predicting chemotherapy-induced nausea and vomiting (CINV) have been assessed in the past, but inconsistencies exist in the literature, studies have methodological shortcomings, and many risk factors have been examined in cross-sectional studies and univariate analyses. To evaluate the predictive power of personal and treatment-related characteristics in the development of CINV, using a large and prospectively evaluated sample of a heterogeneous group of cancer patients receiving routine chemotherapy. This was a multicountry, multisite prospective study over three cycles of chemotherapy. Adult patients from eight European countries about to receive highly and moderately emetogenic chemotherapy were recruited. Clinicians completed a case report form at or before the initial chemotherapy treatment, recording patient demographic and baseline clinical characteristics. Participants completed a daily patient diary for six days per chemotherapy cycle describing their CINV experience. Baseline patient data also included a history of nausea/vomiting (yes/no), patient expectation of nausea (0-100 mm visual analogue scale [VAS]), prechemotherapy anxiety (0-100 mm VAS), and prechemotherapy nausea (0-100 mm VAS) measured during the 24-hour period before chemotherapy initiation. There were 991 evaluable patients with complete Cycle 1 data, 888 for Cycle 2 data, and 769 for Cycle 3 data. A complex picture of predictor variables was shown, with different contribution of variables to the acute, delayed, and overall phases of CINV. Key predictor variables included the use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, and no CINV complete response in an earlier cycle (all at P < 0.05). Anxiety, history of nausea/vomiting, and expectations of nausea were important predictors for some phases and cycles but not consistently across the CINV pathway. The results of this study provide clarity for the relative contribution of a set of characteristics in the development of CINV. Following evidence-based clinical antiemetic guidelines is of paramount importance, alongside treating patients with increased risk for CINV more aggressively, which both could lead to more optimal CINV management. These data can assist clinicians in making decisions about the antiemetic management of their patients.
    No preview · Article · Sep 2013 · Journal of pain and symptom management

Publication Stats

3k Citations
631.17 Total Impact Points

Institutions

  • 2001-2015
    • Hospital Clínic de Barcelona
      • Servicio de Cirugía Torácica
      Barcino, Catalonia, Spain
  • 2005-2014
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      • Division of Oncology and Haematology
      Barcino, Catalonia, Spain
    • Instituto Valenciano de Oncologia
      Valenza, Valencia, Spain
  • 2013
    • Fundació Clínic per a la Recerca Biomèdica
      Barcino, Catalonia, Spain
  • 2012
    • Fundació Recerca
      Barcino, Catalonia, Spain
  • 2009
    • Johns Hopkins University
      Baltimore, Maryland, United States