title: Phase II Trial of Bevacizumab in Combination With Temozolomide as First-Line Treatment in Patients With Metastatic Uveal Melanoma.
abstract: BACKGROUND
  In experimental models, bevacizumab suppressed in vitro growth and in vivo hepatic metastasis of ocular melanoma cells. Additional preclinical data suggested a potential benefit when combining bevacizumab with dacarbazine.
  
  
  METHODS
  This noncomparative phase II study evaluated a combination of bevacizumab (10 mg/kg on days 8 and 22) with temozolomide (150 mg/m(2) on days 1-7 and 15-21) in 36 patients with metastatic uveal melanoma (MUM). The primary endpoint was the progression-free rate (PFR) at 6 months. Using a modified 2-step Fleming plan, at least 10 of 35 patients were required to support a predefined PFR at 6 months of 40%. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety; liver perfusion computed tomography (CT) for response imaging; and impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics.
  
  
  RESULTS
  First- and second-step analyses revealed nonprogression at 6 months in 3 of 17 and 8 of 35 patients, respectively. Finally, the 6-month PFR was 23% (95% confidence interval [CI]: 10-39), with long-lasting stable disease in 5 patients (14%). Median PFS and OS were 12 weeks and 10 months, respectively. No unexpected toxicity occurred. Liver perfusion CT imaging was not useful in assessing tumor response, and VEGF-A gene polymorphisms were not correlated with toxicity or survival.
  
  
  CONCLUSIONS
  In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France sophie.piperno-neumann@curie.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Piperno-Neumann
authors.affiliation: Department of Biostatistics, Institut Curie, Paris, France.
authors.forename: Alhassane
authors.initials: A
authors.lastname: Diallo
authors.affiliation: Onco-Pharmacology Laboratory, Centre Antoine Lacassagne, Nice, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: François-Clément
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodrigues
authors.affiliation: Department of Biostatistics, Institut Curie, Paris, France.
authors.forename: Corine
authors.initials: C
authors.lastname: Plancher
authors.affiliation: Department of Surgical Oncology, Institut Curie, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Mariani
authors.affiliation: Department of Surgical Oncology, Institut Curie, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cassoux
authors.affiliation: Preclinical Investigation Laboratory, Institut Curie, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Decaudin
authors.affiliation: Department of Biostatistics, Institut Curie, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.affiliation: Department of Radiology and Nuclear Medicine, Institut Curie, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Servois
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D055420:Perfusion Imaging; D000077204:Temozolomide; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide