Table Info

Table 2.

Anticancer drugs effects on renal, retinal, neuronal and cardiovascular events

Class	Agents	Adverse outcomes	Mechanisms	References
Nephropathy
mTOR inhibitors	Everolimus Temsirolimus	Increased creatinine Increased UAE	Hyperglycaemia and urinary infections	[67, 104, 105]
Multi-target TKIs	Pazopanib Sunitinib Sorafenib Axitinib	Increased UAE Nephrotic syndrome	Glomerular endothelial damage; Podocyte damage	[67, 104, 107, 108]
Anti-VEGF	Bevacizumab Aflibercept	Increased UAE	Glomerular endothelial damage; Podocyte damage	[104, 107, 108]
ICIs	Ipilimumab Nivolumab Pembrolizumab	Acute interstitial nephritis	Delayed hyper-sensitivity with granulomatous reaction (CD4⁺ T cells and macrophage activation, gamma-interferon production); Podocyte damage	[108–110]
Retinopathy
Anti-oestrogen	Tamoxifen	Retinal exudates and haemorrhages	Retinal thromboembolism	[111–114]
Alkylating agents	Cisplatin Carboplatin Carmustine	Retinal ischaemia and neovascularization	Retinal thrombosis with vascular occlusion (phospholipase A2 and platelet hyperactivation)	[114, 115]
ICIs	Nivolumab	Retinal vessels occlusion Retinal thinning	Autoimmune (abs against retinal proteins)	[116]
Oral anti-VEGF	Pazopanib Sunitinib Sorafenib	Retinal vessels bleeding/occlusion Retinal detachment Macular oedema	Alterations of choroidal vascular permeability; Microvascular events (microemboli)	[119]
MAPK inhibitors	Selumetinib Binimetinib Pimasertib	Retinal vessels occlusion Retinal detachment Subretinal fluid	Alterations of choroidal vascular permeability; Autoimmune (abs against retinal proteins)	[117–120]
Neuropathy
IMIDs	Talidomide	Sensory neuropathy	Inhibition neurotrophic factors (NGF, NF-kB); Reduced angiogenic factors	[121, 122]
Proteasome inhibitor	Bortezomib	Sensory and autonomic neuropathy	Inhibition neurotrophic factors (NF-kB); Autoimmune; miRNA dysregulation (miR-20a, -29b, -34a, -128, -181, -342-3p, -17-92)	[121–123]
Cardiovascular disease
Anthracyclines	Doxorubicin Epirubicin Idarubicin	LV dysfunction/HF	Increased ROS; Mitochondrial dysfunction; Apoptosis	[124, 125, 128, 129]
Anti-HER2 drugs	Trastuzumab Lapatinib Pertuzumab	LV dysfunction/HF Hypertension	ErbB2 inhibition with apoptosis of cardiomyocytes	[124, 125, 128, 130]
Anti-VEGF and Multi-target TKIs	Bevacizumab Pazopanib Sunitinib Sorafenib Vandetanib Regorafenib Axitinib	LV dysfunction/HF Hypertension Myocardial ischemia (rare) Atherosclerosis	NO-mediated dysregulation of endothelial homeostasis	[124, 128]
Anti BCR-ABL1	Imatinib Nilotinib Ponatinib	QTc prolongation HF	Increased ROS; Mitochondrial dysfunction; Cardiomyocytes apoptosis	[124, 128]
ICIs	Ipilimumab Nivolumab Pembrolizumab	Rare cases of: - Myocardial fibrosis - Immune myocarditis - Cardiomyopathy - Acute HF - Lethal myocarditis	Immune-mediated damages^*	[124, 132]
Proteasome inhibitors	Bortezomib Carfilzomib Ixazomib Oprozomib	LV dysfunction Hypertension Myocardial infarction (rare) Cardiac arrest (rare)	Increased ROS; Mitochondrial dysfunction	[128, 131]
Antimetabolites	5-FU Capecitabine Gemcitabine	Coronary spasms/ischemia	Increased ROS; NO reduction; Increased thrombogenicity	[127, 128]
Taxanes	Docetaxel Paclitaxel	Bradycardia LV dysfunction Ischemia	Alteration of tubulin polymerisation and cell division; Stimulation of histamine receptors	[126, 128]

indicates the uncertainty of the evidence on this item; mTOR: mammalian target of rapamycin; UAE: urinary albumin excretion; TKIs: tyrosine kinase inhibitors; VEGF: vascular endothelial growth factor; ICIs: immune checkpoint inhibitors; Abs: antibodies; MAPK: mitogen-activated protein kinase; IMIDs: immunomodulatory drugs; NGF: nerve growth factor; NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells; miRNA: microRNA; LV: left ventricular; HF: heart failure; ROS: reactive oxygen species; HER2: human epidermal growth factor receptor 2; NO: nitric oxide; BCR-ABL: breakpoint cluster region Abelson gene; QTc: corrected QT; 5-FU: 5-Fluorouracil

Declarations

Acknowledgments

The authors gratefully acknowledge professor Giuliana Arcidiacono, English and Anglo-American language PhD., University of Catania, for the language revision of the manuscript.

Author contributions

AM wrote the first draft of the manuscript; PV, FM, RV, and LS wrote sections of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

Not applicable.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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