Subacute cutaneous lupus erythematosus induced by the new multikinase inhibitor pazopanib

Casado-Verrier, Beatriz; Pérez-Santos, Susana; Delgado-Mucientes, Carmen; Beato-Merino, María-José

doi:10.1111/bjd.13175

Cited by 14 publications

(9 citation statements)

References 8 publications

(11 reference statements)

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“…The mechanism was believed to be the combination of c-kit and platelet-derived growth factor inhibition [ 8 ]. Interestingly, a case of pazopanib-induced subacute cutaneous lupus erythematosus has been reported, but the mechanism was unclear [ 9 ]. From our recent finding, it is possible that photosensitivity plays a role.…”

Section: Discussionmentioning

confidence: 99%

Phototoxic Reaction Induced by Pazopanib

2018

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Multikinase inhibitors (MKIs) are a novel target therapy that offers promising long-term survival for patients with advanced-stage cancer. However, they cause a wide range of adverse reactions, skin and skin appendage being the most prevalent. Photosensitivity reactions are well-recognized effects from certain MKIs such as sunitinib and vandetanib. However, phototoxic reaction induced by pazopanib has never been reported. We present here the first case of pazopanib-induced phototoxic drug reaction in a patient with renal cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Phototoxic Reaction Induced by Pazopanib

2018

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“…Pazopanib also shows therapeutic efficacy on non-adipocytic advanced soft tissue sarcoma (Endo & Nielsen, 2012; Sedef et al, 2015; Karch et al, 2016), epithelial ovarian cancer (Dinkic et al, 2017) and non-small cell lung cancer (Koinis et al, 2017). However, adverse effects were frequently reported, including increased liver injury, hypertension and lupus erythematosus (Casado-Verrier et al, 2014). For example, meta-analyses of clinical trials reported that pazopanib is associated with increased risk of liver toxicity (Lim et al, 2013; Rickmann et al, 2013; Jain et al, 2015; Vlenterie et al, 2015; Shantakumar et al, 2016; Choudhury et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

Wang

Yang

Liang³

et al. 2018

Xenobiotica

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To elucidate the metabolism of pazopanib, a metabolomics approach was performed based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry. A total of 22 pazopanib metabolites were identified in vitro and in vivo. Among these metabolites, 17 were novel, including several cysteine adducts and aldehyde derivatives. By screening using recombinant CYPs, CYP3A4 and CYP1A2 were found to be the main forms involved in the pazopanib hydroxylation. Formation of a cysteine conjugate (M3), an aldehyde derivative (M15) and two N-oxide metabolites (M18 and M20) from pazopanib could induce the oxidative stress that may be responsible in part for pazopanib-induced hepatotoxicity. Morphological observation of the liver suggested that pazopanib (300 mg/kg) could cause liver injury. The aspartate transaminase and alanine aminotransferase in serum significantly increased after pazopanib (150, 300 mg/kg) treatment; this liver injury could be partially reversed by the broad-spectrum CYP inhibitor 1-aminobenzotriazole (ABT). Metabolomics analysis revealed that pazopanib could significantly change the levels of L-carnitine, proline and lysophosphatidylcholine 18:1 in liver. Additionally, drug metabolism-related gene expression analysis revealed that hepatic Cyp2d22 and Abcb1a (P-gp) mRNAs were significantly lowered by pazopanib treatment. In conclusion, this study provides a global view of pazopanib metabolism and clues to its influence on hepatic function.

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“…To date, only 3 cases of SCLE induced by targeted therapies have been described, one from the multikinase inhibitor pazopanib and 2 from the antivascular endothelial growth factor monoclonal antibody bevacizumab. 2 Palbociclib is a novel targeted therapy with activity against cyclin-dependent kinases (CDKs) 4 and 6. Cyclin D1 and CDK 4/6 are downstream of multiple signaling pathways, which lead to cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%