title: Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group.
abstract: OBJECTIVE
  Data concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited.
  
  
  METHODS
  This was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses.
  
  
  RESULTS
  The incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043).
  
  
  CONCLUSIONS
  This analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.
authors.affiliation: Royal Marsden Hospital National Health Service Foundation Trust, Surrey and London, United Kingdom.
authors.forename: Naureen
authors.initials: N
authors.lastname: Starling
authors.forename: Sheela
authors.initials: S
authors.lastname: Rao
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.forename: Timothy
authors.initials: T
authors.lastname: Iveson
authors.forename: Marianne
authors.initials: M
authors.lastname: Nicolson
authors.forename: Fareeda
authors.initials: F
authors.lastname: Coxon
authors.forename: Gary
authors.initials: G
authors.lastname: Middleton
authors.forename: Francis
authors.initials: F
authors.lastname: Daniel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Oates
authors.forename: Andrew Richard
authors.initials: AR
authors.lastname: Norman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000069287:Capecitabine; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013923:Thromboembolism / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology* / Q000517:prevention & control; D006113:United Kingdom / Q000453:epidemiology; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D000925:Anticoagulants; D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D015251:Epirubicin; D014859:Warfarin; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil