PURPOSE: The angiogenesis inhibitor pazopanib has been approved for the treatment of advanced renal cell cancer (RCC) and soft tissue sarcoma. Severe and fatal hepatotoxicity has been observed in its clinical studies. This analysis was conducted to determine the risk of liver toxicity by a systematic review and meta-analysis of clinical trials. PATIENTS AND METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meetings up to January, 2012 were searched to identify relevant studies. Eligible studies included prospective trials of cancer patients treated with pazopanib starting at 800 mg daily. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. RESULTS: A total of 1478 patients from 10 clinical trials were included. The incidences of all-grade aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin elevation were 39.6% (95% CI 31.2-48.6%), 41.4% (95% CI 34.1-49.0%), and 24.8% (95% CI 16.3-35.3%), respectively. The incidences of high-grade (Grade 3 and 4) AST, ALT and bilirubin elevation were 6.9% (95% CI 5.5-8.6%), 9.4% (95% CI 7.8-11.4%), and 3.4% (2.4-5.0%), respectively. In comparison with placebo, pazopanib significantly increased the risk of high-grade AST elevation (RR 6.56, 95% CI 2.04-21.07, p = 0.002) and ALT elevation (RR 4.33, 95% CI 1.88-10.0, p = 0.001). However, the risks of high-grade bilirubin elevation (RR 1.31, 95% CI 0.47-3.64) and fatal hepatotoxicity (RR 2.51, 95% CI 0.12-51.91, p = 0.55) were not significantly elevated. CONCLUSION: The use of pazopanib was associated with a significantly increased risk of severe non-fatal hepatotoxicity in cancer patients.
PURPOSE: The angiogenesis inhibitor pazopanib has been approved for the treatment of advanced renal cell cancer (RCC) and soft tissue sarcoma. Severe and fatal hepatotoxicity has been observed in its clinical studies. This analysis was conducted to determine the risk of liver toxicity by a systematic review and meta-analysis of clinical trials. PATIENTS AND METHODS: Databases from PubMed, Web of Science and abstracts presented at ASCO meetings up to January, 2012 were searched to identify relevant studies. Eligible studies included prospective trials of cancerpatients treated with pazopanib starting at 800 mg daily. Summary incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a fixed- or random-effects model. RESULTS: A total of 1478 patients from 10 clinical trials were included. The incidences of all-grade aspartate aminotransferase (AST), alanine transaminase (ALT), and bilirubin elevation were 39.6% (95% CI 31.2-48.6%), 41.4% (95% CI 34.1-49.0%), and 24.8% (95% CI 16.3-35.3%), respectively. The incidences of high-grade (Grade 3 and 4) AST, ALT and bilirubin elevation were 6.9% (95% CI 5.5-8.6%), 9.4% (95% CI 7.8-11.4%), and 3.4% (2.4-5.0%), respectively. In comparison with placebo, pazopanib significantly increased the risk of high-grade AST elevation (RR 6.56, 95% CI 2.04-21.07, p = 0.002) and ALT elevation (RR 4.33, 95% CI 1.88-10.0, p = 0.001). However, the risks of high-grade bilirubin elevation (RR 1.31, 95% CI 0.47-3.64) and fatal hepatotoxicity (RR 2.51, 95% CI 0.12-51.91, p = 0.55) were not significantly elevated. CONCLUSION: The use of pazopanib was associated with a significantly increased risk of severe non-fatal hepatotoxicity in cancerpatients.
Authors: Alexander Kornienko; Antonio Evidente; Maurizio Vurro; Véronique Mathieu; Alessio Cimmino; Marco Evidente; Willem A L van Otterlo; Ramesh Dasari; Florence Lefranc; Robert Kiss Journal: Med Res Rev Date: 2015-04-08 Impact factor: 12.944
Authors: Ana Ezponda; Ignacio González De La Huebra; Marta Calvo; Miguel Ángel Idoate; Isabel Vivas Journal: Oncol Lett Date: 2018-07-10 Impact factor: 2.967
Authors: Lufeng Hu; Fan Wang; Jinzhong Xu; Xiaofang Wang; Hong Lin; Yi Zhang; Yang Yu; Youpei Wang; Lingxia Pang; Xi Zhang; Qi Liu; Guoshi Qiu; Yongsheng Jiang; Longteng Xie; Yanlong Liu Journal: Int J Clin Exp Med Date: 2015-08-15
Authors: Sumitra Shantakumar; Beth L Nordstrom; Luc Djousse; Susan A Hall; David R Gagnon; Kathy H Fraeman; Myrthe van Herk-Sukel; Karen Chagin; Jeanenne Nelson Journal: Cancer Chemother Pharmacol Date: 2016-07-20 Impact factor: 3.333
Authors: Sylvie Négrier; David Pérol; Rastislav Bahleda; Antoine Hollebecque; Etienne Chatelut; Helen Boyle; Philippe Cassier; Séverine Metzger; Ellen Blanc; Jean-Charles Soria; Bernard Escudier Journal: BMC Cancer Date: 2017-08-15 Impact factor: 4.430