title: Venous thromboembolism is a relevant and underestimated adverse event in cancer patients treated in phase I studies.
abstract: BACKGROUND
  To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies.
  
  
  METHODS
  Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered.
  
  
  RESULTS
  Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13-85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29-6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18-8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11-6.30, P=0.028), white blood cell >11,000 μl(-1) (HR: 2.59, 95% CI: 1.10-6.09, P=0.028) and haemoglobin<10 g dl(-1) (HR: 3.1, 95% CI: 1.07-8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02).
  
  
  CONCLUSIONS
  Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs.
authors: Division of Medical Oncology, Department of Oncology and Hematology, Ospedali Riuniti, Largo Barozzi 1, Bergamo 24128, Italy. mariomandala@tin.it
authors: M
authors: M
authors: Mandalà
authors: F
authors: F
authors: Grosso
authors: C
authors: C
authors: Vitalini
authors: I
authors: I
authors: Corradino
authors: R
authors: R
authors: Sanfilippo
authors: S
authors: S
authors: Colombini
authors: M
authors: M
authors: Clerici
authors: R
authors: R
authors: Labianca
authors: A
authors: A
authors: De Pascale
authors: S
authors: S
authors: Marsoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D015994:Incidence; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D012306:Risk; D054556:Venous Thromboembolism / Q000139:chemically induced*; D055815:Young Adult