Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy

Roberto Iacovelli, Antonella Palazzo, Giuseppe Procopio, Matteo Santoni, Patrizia Trenta, Angelina De Benedetto, Silvia Mezi, Enrico Cortesi

Research output: Contribution to journalArticle

Abstract

Aim The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials. Methods PubMed was reviewed for phase III randomized trials with axitinib, pazopanib, sorafenib, sunitinib, regorafenib or vandetanib the characteristics of each study and incidence of all and high grades of ALT, AST and total bilirubin increase were collected. Results A total of 3691 patients was available for meta-analysis, 1170 had metastatic renal cell carcinoma; 950 had advanced non-small cell lung carcinoma, 454 had hepatocarcinoma, 753 had metastatic colorectal cancer and 362 had metastatic soft-tissue sarcoma the incidence of ALT, AST and bilirubin increase of any grade in patients treated with TKIs was 34.0% (95% CI 31.6, 36.3), 39.2% (95% CI 36.7, 41.6) and 21.8% (95% CI 19.9, 23.7), respectively the incidence of the high grade increase was 5.2% (95% CI 4.2, 6.4), 5.0% (95% CI, 3.8, 6.2) and 1.7% (95% CI 1.1, 2.4), respectively the relative risk of ALT, AST and total bilirubin increase was 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively. Conclusions Hepatotoxicity is a relative common event occurring in 23-40% of patients treated with TKIs. Despite this, only 5% of patients have had high grade of toxicity. A better knowledge of this phenomenon may prevent high grade toxicity and reduce treatment discontinuation due to this adverse event.

Original languageEnglish
Pages (from-to)929-938
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Volume77
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Protein-Tyrosine Kinases
Bilirubin
Liver
Incidence
Neoplasms
Meta-Analysis
Renal Cell Carcinoma
PubMed
Non-Small Cell Lung Carcinoma
Sarcoma
Colorectal Neoplasms
Cohort Studies
Clinical Trials
Therapeutics

Keywords

  • pazopanib
  • regorafenib
  • renal cell carcinoma
  • soft tissue sarcoma
  • sorafenib
  • sunitinib

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Medicine(all)

Cite this

Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy. / Iacovelli, Roberto; Palazzo, Antonella; Procopio, Giuseppe; Santoni, Matteo; Trenta, Patrizia; De Benedetto, Angelina; Mezi, Silvia; Cortesi, Enrico.

In: British Journal of Clinical Pharmacology, Vol. 77, No. 6, 2014, p. 929-938.

Research output: Contribution to journalArticle

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abstract = "Aim The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials. Methods PubMed was reviewed for phase III randomized trials with axitinib, pazopanib, sorafenib, sunitinib, regorafenib or vandetanib the characteristics of each study and incidence of all and high grades of ALT, AST and total bilirubin increase were collected. Results A total of 3691 patients was available for meta-analysis, 1170 had metastatic renal cell carcinoma; 950 had advanced non-small cell lung carcinoma, 454 had hepatocarcinoma, 753 had metastatic colorectal cancer and 362 had metastatic soft-tissue sarcoma the incidence of ALT, AST and bilirubin increase of any grade in patients treated with TKIs was 34.0{\%} (95{\%} CI 31.6, 36.3), 39.2{\%} (95{\%} CI 36.7, 41.6) and 21.8{\%} (95{\%} CI 19.9, 23.7), respectively the incidence of the high grade increase was 5.2{\%} (95{\%} CI 4.2, 6.4), 5.0{\%} (95{\%} CI, 3.8, 6.2) and 1.7{\%} (95{\%} CI 1.1, 2.4), respectively the relative risk of ALT, AST and total bilirubin increase was 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively. Conclusions Hepatotoxicity is a relative common event occurring in 23-40{\%} of patients treated with TKIs. Despite this, only 5{\%} of patients have had high grade of toxicity. A better knowledge of this phenomenon may prevent high grade toxicity and reduce treatment discontinuation due to this adverse event.",
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T1 - Incidence and relative risk of hepatic toxicity in patients treated with anti-angiogenic tyrosine kinase inhibitors for malignancy

AU - Iacovelli, Roberto

AU - Palazzo, Antonella

AU - Procopio, Giuseppe

AU - Santoni, Matteo

AU - Trenta, Patrizia

AU - De Benedetto, Angelina

AU - Mezi, Silvia

AU - Cortesi, Enrico

PY - 2014

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N2 - Aim The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials. Methods PubMed was reviewed for phase III randomized trials with axitinib, pazopanib, sorafenib, sunitinib, regorafenib or vandetanib the characteristics of each study and incidence of all and high grades of ALT, AST and total bilirubin increase were collected. Results A total of 3691 patients was available for meta-analysis, 1170 had metastatic renal cell carcinoma; 950 had advanced non-small cell lung carcinoma, 454 had hepatocarcinoma, 753 had metastatic colorectal cancer and 362 had metastatic soft-tissue sarcoma the incidence of ALT, AST and bilirubin increase of any grade in patients treated with TKIs was 34.0% (95% CI 31.6, 36.3), 39.2% (95% CI 36.7, 41.6) and 21.8% (95% CI 19.9, 23.7), respectively the incidence of the high grade increase was 5.2% (95% CI 4.2, 6.4), 5.0% (95% CI, 3.8, 6.2) and 1.7% (95% CI 1.1, 2.4), respectively the relative risk of ALT, AST and total bilirubin increase was 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively. Conclusions Hepatotoxicity is a relative common event occurring in 23-40% of patients treated with TKIs. Despite this, only 5% of patients have had high grade of toxicity. A better knowledge of this phenomenon may prevent high grade toxicity and reduce treatment discontinuation due to this adverse event.

AB - Aim The aim of this study is to investigate the incidence and risk of hepatic toxicity in patients receiving tyrosine kinase inhibitors (TKIs) through a large up-to-date meta-analysis of available clinical trials. Methods PubMed was reviewed for phase III randomized trials with axitinib, pazopanib, sorafenib, sunitinib, regorafenib or vandetanib the characteristics of each study and incidence of all and high grades of ALT, AST and total bilirubin increase were collected. Results A total of 3691 patients was available for meta-analysis, 1170 had metastatic renal cell carcinoma; 950 had advanced non-small cell lung carcinoma, 454 had hepatocarcinoma, 753 had metastatic colorectal cancer and 362 had metastatic soft-tissue sarcoma the incidence of ALT, AST and bilirubin increase of any grade in patients treated with TKIs was 34.0% (95% CI 31.6, 36.3), 39.2% (95% CI 36.7, 41.6) and 21.8% (95% CI 19.9, 23.7), respectively the incidence of the high grade increase was 5.2% (95% CI 4.2, 6.4), 5.0% (95% CI, 3.8, 6.2) and 1.7% (95% CI 1.1, 2.4), respectively the relative risk of ALT, AST and total bilirubin increase was 1.85, 2.19 and 1.79 for any grade and 2.75, 2.39 and 1.65 for high grade, respectively. Conclusions Hepatotoxicity is a relative common event occurring in 23-40% of patients treated with TKIs. Despite this, only 5% of patients have had high grade of toxicity. A better knowledge of this phenomenon may prevent high grade toxicity and reduce treatment discontinuation due to this adverse event.

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