Severe hepatic dysfunction is associated with venous thromboembolic events in phase 1 clinical trials

Aaron Mansfield, A. J. Tafur, D. Vulih, G. L. Smith, P. J. Harris, S. P. Ivy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Introduction Venous thromboembolic events (VTEs) are a significant cause of death in patients with cancer. The incidence of VTE is not well characterized in early phase clinical trials of novel antineoplastic agents, or in hepatic dysfunction studies designed for patients with varying degrees of liver test abnormalities. We compared the incidences of VTE in phase 1 clinical trials (P1CTs) and hepatic dysfunction trials (HDCTs) sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) of the United States. Materials & methods We reviewed individual patient records of 1841 subjects for symptomatic VTE diagnosed while on study: 1328 subjects on 42 P1CTs, and 513 subjects on 9 HDCTs. The NCI's Organ Dysfunction Working Group definitions were used to categorize patients. The incidences of VTEs between patients were compared by the Chi square test. Confounders were evaluated with the Cochran-Mantel-Haenszel method. Results & conclusions There were 43 VTEs identified among all subjects (2.3%). There were significantly more VTE observed in the subjects on P1CTs (n = 38, 2.9%) than in the subjects on HDCTs (n = 5, 1.0%; RR 0.341, 95% 0.13-0.86, p = 0.015). For patients on HDCTs, those with severe dysfunction had a high incidence of VTE (RR 10.5 (1.12-93.6), p = 0.021) that remained significant in a multivariate model. VTEs were observed less frequently in patients who were enrolled in HDCT than those who were enrolled in P1CT; however, patients with severe hepatic dysfunction were more likely to experience VTE. Severe liver test abnormalities may not be protective against VTE in patients with malignancies receiving chemotherapy.

Original languageEnglish (US)
Pages (from-to)1169-1173
Number of pages5
JournalThrombosis Research
Volume136
Issue number6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Clinical Trials, Phase I
Liver
Incidence
Neoplasms
National Cancer Institute (U.S.)
Program Evaluation
Chi-Square Distribution
Antineoplastic Agents
Cause of Death
Clinical Trials
Drug Therapy

Keywords

  • Clinical trials, phase 1
  • Liver diseases
  • Neoplasms
  • Pulmonary embolism
  • Venous thrombosis

ASJC Scopus subject areas

  • Hematology

Cite this

Severe hepatic dysfunction is associated with venous thromboembolic events in phase 1 clinical trials. / Mansfield, Aaron; Tafur, A. J.; Vulih, D.; Smith, G. L.; Harris, P. J.; Ivy, S. P.

In: Thrombosis Research, Vol. 136, No. 6, 01.12.2015, p. 1169-1173.

Research output: Contribution to journalArticle

Mansfield, Aaron ; Tafur, A. J. ; Vulih, D. ; Smith, G. L. ; Harris, P. J. ; Ivy, S. P. / Severe hepatic dysfunction is associated with venous thromboembolic events in phase 1 clinical trials. In: Thrombosis Research. 2015 ; Vol. 136, No. 6. pp. 1169-1173.
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abstract = "Introduction Venous thromboembolic events (VTEs) are a significant cause of death in patients with cancer. The incidence of VTE is not well characterized in early phase clinical trials of novel antineoplastic agents, or in hepatic dysfunction studies designed for patients with varying degrees of liver test abnormalities. We compared the incidences of VTE in phase 1 clinical trials (P1CTs) and hepatic dysfunction trials (HDCTs) sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) of the United States. Materials & methods We reviewed individual patient records of 1841 subjects for symptomatic VTE diagnosed while on study: 1328 subjects on 42 P1CTs, and 513 subjects on 9 HDCTs. The NCI's Organ Dysfunction Working Group definitions were used to categorize patients. The incidences of VTEs between patients were compared by the Chi square test. Confounders were evaluated with the Cochran-Mantel-Haenszel method. Results & conclusions There were 43 VTEs identified among all subjects (2.3{\%}). There were significantly more VTE observed in the subjects on P1CTs (n = 38, 2.9{\%}) than in the subjects on HDCTs (n = 5, 1.0{\%}; RR 0.341, 95{\%} 0.13-0.86, p = 0.015). For patients on HDCTs, those with severe dysfunction had a high incidence of VTE (RR 10.5 (1.12-93.6), p = 0.021) that remained significant in a multivariate model. VTEs were observed less frequently in patients who were enrolled in HDCT than those who were enrolled in P1CT; however, patients with severe hepatic dysfunction were more likely to experience VTE. Severe liver test abnormalities may not be protective against VTE in patients with malignancies receiving chemotherapy.",
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T1 - Severe hepatic dysfunction is associated with venous thromboembolic events in phase 1 clinical trials

AU - Mansfield, Aaron

AU - Tafur, A. J.

AU - Vulih, D.

AU - Smith, G. L.

AU - Harris, P. J.

AU - Ivy, S. P.

PY - 2015/12/1

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N2 - Introduction Venous thromboembolic events (VTEs) are a significant cause of death in patients with cancer. The incidence of VTE is not well characterized in early phase clinical trials of novel antineoplastic agents, or in hepatic dysfunction studies designed for patients with varying degrees of liver test abnormalities. We compared the incidences of VTE in phase 1 clinical trials (P1CTs) and hepatic dysfunction trials (HDCTs) sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) of the United States. Materials & methods We reviewed individual patient records of 1841 subjects for symptomatic VTE diagnosed while on study: 1328 subjects on 42 P1CTs, and 513 subjects on 9 HDCTs. The NCI's Organ Dysfunction Working Group definitions were used to categorize patients. The incidences of VTEs between patients were compared by the Chi square test. Confounders were evaluated with the Cochran-Mantel-Haenszel method. Results & conclusions There were 43 VTEs identified among all subjects (2.3%). There were significantly more VTE observed in the subjects on P1CTs (n = 38, 2.9%) than in the subjects on HDCTs (n = 5, 1.0%; RR 0.341, 95% 0.13-0.86, p = 0.015). For patients on HDCTs, those with severe dysfunction had a high incidence of VTE (RR 10.5 (1.12-93.6), p = 0.021) that remained significant in a multivariate model. VTEs were observed less frequently in patients who were enrolled in HDCT than those who were enrolled in P1CT; however, patients with severe hepatic dysfunction were more likely to experience VTE. Severe liver test abnormalities may not be protective against VTE in patients with malignancies receiving chemotherapy.

AB - Introduction Venous thromboembolic events (VTEs) are a significant cause of death in patients with cancer. The incidence of VTE is not well characterized in early phase clinical trials of novel antineoplastic agents, or in hepatic dysfunction studies designed for patients with varying degrees of liver test abnormalities. We compared the incidences of VTE in phase 1 clinical trials (P1CTs) and hepatic dysfunction trials (HDCTs) sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) of the United States. Materials & methods We reviewed individual patient records of 1841 subjects for symptomatic VTE diagnosed while on study: 1328 subjects on 42 P1CTs, and 513 subjects on 9 HDCTs. The NCI's Organ Dysfunction Working Group definitions were used to categorize patients. The incidences of VTEs between patients were compared by the Chi square test. Confounders were evaluated with the Cochran-Mantel-Haenszel method. Results & conclusions There were 43 VTEs identified among all subjects (2.3%). There were significantly more VTE observed in the subjects on P1CTs (n = 38, 2.9%) than in the subjects on HDCTs (n = 5, 1.0%; RR 0.341, 95% 0.13-0.86, p = 0.015). For patients on HDCTs, those with severe dysfunction had a high incidence of VTE (RR 10.5 (1.12-93.6), p = 0.021) that remained significant in a multivariate model. VTEs were observed less frequently in patients who were enrolled in HDCT than those who were enrolled in P1CT; however, patients with severe hepatic dysfunction were more likely to experience VTE. Severe liver test abnormalities may not be protective against VTE in patients with malignancies receiving chemotherapy.

KW - Clinical trials, phase 1

KW - Liver diseases

KW - Neoplasms

KW - Pulmonary embolism

KW - Venous thrombosis

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