title: Bevacizumab combined with 5-FU/streptozocin in patients with progressive metastatic well-differentiated pancreatic endocrine tumours (BETTER trial)--a phase II non-randomised trial.
abstract: OBJECTIVE
  Neuroendocrine tumours are highly vascular neoplasms known to overexpress vascular endothelial growth factor (VEGF) and its receptor. Bevacizumab, an inhibitor of VEGF, was assessed in combination with chemotherapy in pancreatic neuroendocrine tumour (P-NET).
  
  
  METHODS
  BETTER was a multicentre, open-label, non-randomised, two-group phase II trial. Patients with progressive metastatic, well-differentiated P-NET received a minimum of 6 month treatment of bevacizumab at 7.5 mg/kg IV on d1 q3w with 5-FU at 400 mg/m2/day and streptozocin at 500 mg/m2/day IV from d1 to d5 every 42 days. The primary end-point was progression-free survival (PFS); secondary end-points were overall survival (OS), overall response rate, safety and quality of life.
  
  
  RESULTS
  A total of 34 patients were included. Median age was 55 years, 65% of patients were men, 97% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and 97% had a Ki-67 proliferative index of <15%. After a maximum of 24 month follow-up per patient, the median PFS assessed by investigators was 23.7 months [95% confidence interval (CI): 13.1; not reached], 19 (56%) patients had a partial response and 15 (44%) had stable disease as best response. OS rate at 24 months was 88%. The most frequently reported grade 3-4 adverse events were hypertension (21% patients), abdominal pain (12%) and thromboembolic events (9%).
  
  
  CONCLUSIONS
  Bevacizumab with 5-FU/streptozocin in the treatment of pancreatic NETs seems to be feasible with a PFS of 23.7 months, which deserves further attention. No unexpected toxicity was observed.
authors.affiliation: Gastrointestinal Oncology Department, Gustave Roussy Institute, Villejuif, France; Faculté de Médecine, Paris Sud Uiversty Le Kremlin Bicêtre, France. Electronic address: Michel.DUCREUX@igr.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.affiliation: Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: laetitia.dahan@mail.hp-hm.fr.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Dahan
authors.affiliation: Medical Oncology Department, Saint-André Hospital, Bordeaux, France. Electronic address: denis.smith@chu-bordeaux.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Smith
authors.affiliation: Clinical Medicine and Gastroenterology Department, St James's Hospital and Trinity College, Dublin, Ireland. Electronic address: OTOOLED1@tcd.ie.
authors.forename: Dermot
authors.initials: D
authors.lastname: O'Toole
authors.affiliation: Medical Oncology Department, Georges Pompidou European Hospital, Paris, France. Electronic address: celine.lepere@egp.aphp.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Lepère
authors.affiliation: Radio Diagnostic Department, Gustave Roussy Institute, Villejuif, France. Electronic address: dromain@igr.fr.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Dromain
authors.affiliation: Radiology Department, Beaujon Hospital, Clichy, France. Electronic address: valerie.vilgrain@bjn.aphp.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilgrain
authors.affiliation: Nuclear Medicine and Endocrine Oncology Department, Gustave Roussy Institute, Villejuif, France. Electronic address: Eric.BAUDIN@igr.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.affiliation: Medical Oncology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: catherine.lombard-bohas@chu-lyon.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lombard-Bohas
authors.affiliation: Pathology Department, Edouard Herriot Hospital, Lyon, France. Electronic address: jy.scoazec@gmail.com.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Scoazec
authors.affiliation: Gastrointestinal Oncology Department, La Timone Hospital, Aix-Marseille Université, Marseille, France. Electronic address: Jean-francois.SEITZ@ap-hm.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.affiliation: Clinial Operating Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: laurence.bitoun@roche.com.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bitoun
authors.affiliation: Oncology Department, Roche Laboratories, Boulogne-Billancourt, France. Electronic address: sebastien.kone@roche.com.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Koné
authors.affiliation: Medical Oncology Department, Curie Institute, Paris, France. Electronic address: emmanuel.mitry@curie.net.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mitry
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D013311:Streptozocin; D005472:Fluorouracil
keywords: 5-FU; Bevacizumab; Metastatic; Pancreatic neuroendocrine tumours; Streptozocin