title: A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites.
abstract: OBJECTIVE
  The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.
  
  
  METHODS
  Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2 weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.
  
  
  RESULTS
  Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%-84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0-178.0) days, which was 4.5 times longer than the baseline interval (16.8 days). Median progression-free survival was 59.5 (95% CI 41.0-83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).
  
  
  CONCLUSIONS
  Aflibercept 4mg/kg every 2 weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.
authors: Istituto Europeo di Oncologia, Divisione di Ginecologia, Via Ripamonti, Milano, Italy. nicoletta.colombo@ieo.it
authors: Nicoletta
authors: N
authors: Colombo
authors: Giorgia
authors: G
authors: Mangili
authors: Serafina
authors: S
authors: Mammoliti
authors: Mårten
authors: M
authors: Kalling
authors: Bengt
authors: B
authors: Tholander
authors: Lars
authors: L
authors: Sternas
authors: Giliane
authors: G
authors: Buzenet
authors: Donald
authors: D
authors: Chamberlain
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000401:mortality; D000328:Adult; D000368:Aged; D001201:Ascites / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy; D000077216:Carcinoma, Ovarian Epithelial; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000150:complications / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000150:complications* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000150:complications* / Q000401:mortality; D019152:Paracentesis; D010534:Peritoneal Neoplasms / Q000150:complications / Q000401:mortality; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
chemical_list: D011993:Recombinant Fusion Proteins; D042442:Vascular Endothelial Growth Factors; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor