title: Combination of Carboplatin and Bevacizumab Is an Efficient Therapeutic Approach in Retinoblastoma Patient-Derived Xenografts.
abstract: OBJECTIVE
  Retinoblastoma (Rb) is a rare childhood cancer of the retina with a survival rate of 95% in children living in high-income countries, after appropriate therapies such as chemotherapy, local ophthalmologic treatment, and radiotherapy. However, due to inactivation of the RB1 gene, all bilateral and almost 15% of unilateral retinoblastoma patients have a higher risk of s econdary cancers, especially sarcomas. Hence, new nonmutagen treatments are warranted. Therefore, we investigated the efficacy of therapy using anti-VEGF antibody bevacizumab, either alone or with carboplatin, in well-characterized Rb patient-derived xenografts (PDXs).
  
  
  METHODS
  Three Rb PDXs previously established and characterized, RB102, RB111, and RB200, have been treated using carboplatin, bevacizumab, or carboplatin + bevacizumab. In order to define antitumor responses, various quantitative PCR and histopathologic analyses have then been performed on tumors collected at the end of experiments.
  
  
  RESULTS
  In all treated PDX models, we have observed a high and significant improvement of chemotherapy-induced in vivo efficacy by the antiangiogenic antibody. The overall response rate, lower than -0.5, was 48%, 27%, and 86% after carboplatin, bevacizumab, and carboplatin + bevacizumab, respectively (carboplatin versus carboplatin + bevacizumab; P < 10-2; bevacizumab versus carboplatin + bevacizumab; P < 10-3). In the Rb200 PDX, such a result was also observed when bevacizumab was combined with lower doses of carboplatin. Quantitative PCR and histopathologic analyses have been performed and confirmed the impact of the bevacizumab-based treatments on various angiogenic markers.
  
  
  CONCLUSIONS
  Overall, our in vivo results confirm the interest in antiangiogenic therapy for the treatment of Rb in combination with carboplatin and provide a robust rationale for testing this combination in the clinical setting for Rb patients.
authors.affiliation: Laboratory of Preclinical Investigation, Translational Research Department, Paris Sciences et Lettres (PSL) University, Institut Curie, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Assayag
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dehainault
authors.affiliation: Department of Genetics, Institut Curie, Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Meseure
authors.affiliation: Department of Pediatric and Young Adult Oncology, Institut Curie, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aerts
authors.affiliation: Department of Surgical Oncology and Ophthalmology, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Department of Genetics, Institut Curie, Paris, France 6INSERM U830, Research Centre, Institut Curie, Paris Sciences et Lettres (PSL) University, Paris, France 7Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Houdayer
authors.affiliation: Department of Pediatric and Young Adult Oncology, Institut Curie, Paris, France 7Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.affiliation: Laboratory of Preclinical Investigation, Translational Research Department, Paris Sciences et Lettres (PSL) University, Institut Curie, Paris, France 8Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin