title: Incidence and clinical implications of venous thromboembolism in advanced colorectal cancer patients: the 'GISCAD-alternating schedule' study findings.
abstract: OBJECTIVE
  To investigate the incidence and clinical implications of venous thromboembolism (VTE) in advanced colorectal cancer (ACC) patients treated and followed-up through a prospective randomised trial, comparing FOLFIRI chemotherapy given as an intermittent or as a continuous schedule.
  
  
  METHODS
  A total of 266 patients were randomised by 15 experimental centres: 168 (63.2%) were males, median age: 64.6 years, age range: 37-76 years. Almost all (95.5%) patients had metastatic disease, while the remainder were classified with locally advanced irresectable disease. For 138 (51.9%) of the patients, the chemotherapy treatment was intermittent FOLFIRI and the remaining patients received continuous treatment. All toxicities, including VTE, were prospectively collected.
  
  
  RESULTS
  During the study protocol, the central data management gathered two cases of VTE. Our analysis retrieved 27 (10.2%) patients who developed a VTE, almost all (89%) during the course of chemotherapy treatment: 20 out of 27 during FOLFIRI, the remaining 7 during following lines or follow-up. VTE was the most frequent grade 3/4 toxicity. The incidence of VTE was significantly increased in the patients receiving continuous rather than intermittent treatment (HR 2.67, 95% CI 1.17-6.10; p<0.02).
  
  
  CONCLUSIONS
  VTE is a common complication among advanced colorectal cancer patients and yet this type of toxicity is widely underestimated. In this randomised trial, VTE was the most frequent grade 3/4 toxicity. Use of an intermittent schedule is associated with a reduced risk of developing VTE.
authors.affiliation: Unit of Medical Oncology, Ospedali Riuniti, Bergamo, Italy. mariomandala@tin.it
authors.forename: Mario
authors.initials: M
authors.lastname: Mandalà
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.forename: Luciano
authors.initials: L
authors.lastname: Isa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fornarini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Marangolo
authors.forename: Stefania
authors.initials: S
authors.lastname: Mosconi
authors.forename: Domenico
authors.initials: D
authors.lastname: Corsi
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.forename: Luciano
authors.initials: L
authors.lastname: Frontini
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D054556:Venous Thromboembolism / Q000150:complications* / Q000401:mortality
chemical_list: D002955:Leucovorin; D005472:Fluorouracil