A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).

Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal...

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Publicado en:BMC Cancer Vol. 15; no. 1; pp. 69 - 70
Autores principales: Avallone, Antonio, Piccirillo, Maria Carmela, Aloj, Luigi, Nasti, Guglielmo, Delrio, Paolo, Izzo, Francesco, Di Gennaro, Elena, Tatangelo, Fabiana, Granata, Vincenza, Cavalcanti, Ernesta, Maiolino, Piera, Bianco, Francesco, Aprea, Pasquale, De Bellis, Mario, Pecori, Biagio, Rosati, Gerardo, Carlomagno, Chiara, Bertolini, Alessandro, Gallo, Ciro, Romano, Carmela
Formato: research randomized controlled trial Journal Article
Publicado: BioMed Central 2015
Acceso en línea:Ver este registro en EBSCOhost
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      pub: BioMed Central
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        10.1186/s12885-016-2102-y
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        atl: A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer-OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme).
      aug:
        au:
          Avallone, Antonio
          Piccirillo, Maria Carmela
          Aloj, Luigi
          Nasti, Guglielmo
          Delrio, Paolo
          Izzo, Francesco
          Di Gennaro, Elena
          Tatangelo, Fabiana
          Granata, Vincenza
          Cavalcanti, Ernesta
          Maiolino, Piera
          Bianco, Francesco
          Aprea, Pasquale
          De Bellis, Mario
          Pecori, Biagio
          Rosati, Gerardo
          Carlomagno, Chiara
          Bertolini, Alessandro
          Gallo, Ciro
          Romano, Carmela
        affil: Multidisciplinary Treatment Unit, Gastrointestinal Medical Oncology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy
      sug:
        subj:
          Colorectal Neoplasms Drug Therapy
          Antineoplastic Agents, Combined Administration and Dosage
          Leucovorin Administration and Dosage
          Vascular Endothelial Growth Factor A Immunology
          Middle Age
          Colorectal Neoplasms Pathology
          Antibodies, Monoclonal Administration and Dosage
          Antibodies, Monoclonal Adverse Effects
          Prognosis
          Human
          Antineoplastic Agents, Combined Adverse Effects
          Organoplatinum Compounds Administration and Dosage
          Female
          Adult
          Aged
          Male
          Fluorouracil Administration and Dosage
          Vascular Endothelial Growth Factor A
          Vascular Endothelial Growth Factor A Antagonists and Inhibitors
          Clinical Trials
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Randomized Controlled Trials
          Middle Aged: 45-64 years
          Adult: 19-44 years
          Aged: 65+ years
          Female
          Male
      ab: Background: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy.Methods/design: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project.Discussion: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873.
      pubtype: Academic Journal
      doctype:
        research
        randomized controlled trial
        Journal Article
      ougenre: Article
    language: English
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