title: Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach.
abstract: OBJECTIVE
  To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo.
  
  
  METHODS
  Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies.
  
  
  RESULTS
  Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10).
  
  
  CONCLUSIONS
  We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.
authors: Weill Cornell Medical College, New York, NY, USA.
authors: Allyson J
authors: AJ
authors: Ocean
authors: Paul
authors: P
authors: Christos
authors: Joseph A
authors: JA
authors: Sparano
authors: Manish A
authors: MA
authors: Shah
authors: Rhonda K
authors: RK
authors: Yantiss
authors: Jonathan
authors: J
authors: Cheng
authors: Juan
authors: J
authors: Lin
authors: Michael
authors: M
authors: Papetti
authors: Dan
authors: D
authors: Matulich
authors: Felice
authors: F
authors: Schnoll-Sussman
authors: Christen
authors: C
authors: Besanceney-Webler
authors: Jenny
authors: J
authors: Xiang
authors: Maureen
authors: M
authors: Ward
authors: Kaili Temple
authors: KT
authors: Dilts
authors: Roger
authors: R
authors: Keresztes
authors: Shannon
authors: S
authors: Holloway
authors: Eric X
authors: EX
authors: Chen
authors: John J
authors: JJ
authors: Wright
authors: Maureen E
authors: ME
authors: Lane
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D061988:Proteasome Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics
chemical_list: D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D000077146:Irinotecan; D002166:Camptothecin