Abstract
The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. Compared to other advanced tumors, the treatment of renal cancer is highly affected by impaired renal function; therefore, patients with severe renal insufficiency, including patients on hemodialysis, are generally excluded from clinical trials. In the present manuscript we present the case of a renal cancer patient who underwent bilateral nephrectomy and received two lines of treatment. We hypothesized that axitinib, a tyrosine kinase inhibitor, would have a similar plasma concentration to patients without hemodialysis and that the levels before and after hemodiafiltration will not differ significantly, as observed in other targeted therapies. The observed axitinib concentrations were at least an order of magnitude lower than expected based on the literature and measurements in other patients. The present case report indicates a potential risk of axitinib underdosing in patients on hemodiafiltration with the standard dose; therefore, drug dosage may need to be corrected based on the plasma levels of axitinib.
Highlights
Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignant tumors, with Czech Republic presenting the highest RCC incidence and mortality rates[1]
Compared with other advanced tumors, the proportion of patients with renal impairment and/or chronic renal failure is high in metastatic RCC (mRCC) due to age, comorbidities, and a high proportion of patients with prior nephrectomy or even bilateral nephrectomy, in some cases the patients are dependent on hemodialysis for life. mRCC patients with severe renal failure, in particular those on hemodialysis, pose a therapeutic challenge to medical oncologists, as the registration trials of targeted therapy did not include patients with severe renal dysfunction
We present the case of a patient who underwent bilateral nephrectomy for RCC, received axitinib in the second line and its plasmatic levels monitored while on hemodiafiltration
Summary
Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignant tumors, with Czech Republic presenting the highest RCC incidence and mortality rates[1]. The standard treatment for metastatic RCC (mRCC), in addition to cytoreductive nephrectomy or the less common metastasectomy, is currently based on the vascular endothelial growth factor (VEGF) antibody bevacizumab, tyrosine kinase inhibitors (TKI) targeting VEGF receptors such as sorafenib, sunitinib, pazopanib, cabozantinib, lenvatinib and axitinib, mammalian target of rapamycin (mTOR) inhibitors temsirolimus and everolimus, cytokines (interferon-α and interleukin-2) or nivolumab. We present the case of a patient who underwent bilateral nephrectomy for RCC, received axitinib in the second line and its plasmatic levels monitored while on hemodiafiltration. The standard treatment for metastatic renal cancer is based on vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTor) inhibitors. A tyrosine kinase inhibitor, would have a similar plasma concentration to patients without hemodialysis and that the levels before and after hemodiafiltration will not differ significantly, as observed in other targeted therapies. The present case report indicates a potential risk of axitinib underdosing in patients on hemodiafiltration with the standard dose; drug dosage may need to be corrected based on the plasma levels of axitinib
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