title: A phase I trial of bortezomib in combination with epirubicin, carboplatin and capecitabine (ECarboX) in advanced oesophagogastric adenocarcinoma.
abstract: OBJECTIVE
  The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy.
  
  
  METHODS
  A Phase I dose-escalation study was performed administering bortezomib (0.7, 1.0, 1.3 and 1.6 mg m(-2) on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m(-2) intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m(-2) BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma. The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX.
  
  
  RESULTS
  18 patients received bortezomib 0.7 (n = 6), 1.0 (n = 3), 1.3 (n = 6) and 1.6 mg m(-2) (n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m(-2) BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3 %), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for >8 weeks.
  
  
  CONCLUSIONS
  The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy.
authors.affiliation: Northern Ireland Cancer Centre, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, Northern Ireland, UK, rturkington01@qub.ac.uk.
authors.forename: R C
authors.initials: RC
authors.lastname: Turkington
authors.forename: C
authors.initials: C
authors.lastname: Purcell
authors.forename: C R
authors.initials: CR
authors.lastname: James
authors.forename: J
authors.initials: J
authors.lastname: Millar
authors.forename: E
authors.initials: E
authors.lastname: Napier
authors.forename: D
authors.initials: D
authors.lastname: Law
authors.forename: R
authors.initials: R
authors.lastname: Gallagher
authors.forename: M
authors.initials: M
authors.lastname: Morris
authors.forename: R H
authors.initials: RH
authors.lastname: Wilson
authors.forename: M M
authors.initials: MM
authors.lastname: Eatock
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D061988:Proteasome Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D003841:Deoxycytidine; D015251:Epirubicin; D000069286:Bortezomib; D016190:Carboplatin