Multi-Targeted Tyrosine Kinase Inhibitor-Induced Hyperammonemic Encephalopathy: a Report of Two Cases Using Pazopanib, Sunitinib, and Regorafenib

Excerpt

With the development of targeted therapies in the past decades, new side effects in relation to the mechanism of the therapies have surfaced. Several drugs were terminated in the early phases of clinical development due to unanticipated toxicities [1]. Currently in clinical practice, targeted therapies, such as tyrosine kinase inhibitors (TKIs), have become widely used for treatment of several malignancies. Physicians are now increasingly challenged to manage the undesired adverse effects to maximize the clinical benefits of these drugs for their patients. The common adverse effects of multi-targeted TKIs reported in clinical studies include hand-foot syndrome, diarrhea, hypertension, and metabolic and electrolyte imbalance [1]. These common toxicities were reported as a class effect of multi-targeted TKI, such as sorafenib, sunitinib, pazopanib, and regorafenib, due to the class-specific mechanism. However, other uncommon adverse effects are typically underreported before approval of these drugs. Therefore, physicians could potentially be faced with these uncommon toxicities in clinical practice. …