Renal Toxicities of Targeted Therapies

Abstract

With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort

“…The persistence of an abnormal albumin:creatinine ratio in one of the patients nine months following treatment cessation implies long-term nephrotoxicity is a significant concern. Renal biopsy reports in patients with bevacizumab associated proteinuria are sparse but the most commonly described change is of glomerular thrombotic microangiopathic change [19]. As NF2 patients have a higher rate of hypertension than age matched controls, exposure to bevacizumab may further increase that risk and this may account for why rates are similar to older general oncology populations [16].…”

Comorbidity in older adults with cancer

“…(28) In addition, as cancer treatment can result in new comorbidities, such as cardiac toxicity, neuropathy, or renal impairment, it is important to distinguish pre-treatment comorbid conditions from those that develop as a consequence of toxicity. (29, 30)…”

Imatinib mesylate-induced kidney injury in the treatment of a gastrointestinal stromal tumor

“…[11,14] In these studies, the most common adverse events were edema (74%), nausea (52%), diarrhea (45%), and musculoskeletal pain (40%). There have been reports of renal toxicities with target-based therapies in the past [20] and specifically with imatinib, [21] but all within in the CML population. The molecular mechanism behind the imatinib-induced nephrotoxicity has not been fully elucidated.…”