Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cell Carcinoma: Focus on Pazopanib

Abstract

Advances in our understanding of renal cancer biology have led to a new treatment paradigm in renal cancer. Tyrosine kinase inhibitors (TKI), that target the intracellular kinase domain of the VEGF receptor, have become established as the most successful class of agent in this disease. Three TKIs are currently approved for use in patients with advanced disease. Newer, more potent inhibitors have reached phase III clinical testing, meaning others are likely to follow. In 2009, pazopanib became the most recent TKI to receive FDA approval. This review sets out to discuss the key opportunities and challenges associated with TKI use in RCC, focusing particularly on pazopanib. We also review the current place of pazopanib in the management of patients with advanced disease, in what is a rapidly evolving therapeutic landscape.

Dynamic Tissue Perfusion Measurement: A New Tool for Characterizing Renal Perfusion in Renal Cell Carcinoma Patients

“…Hereby, the overexpression of proangiogenic factors and intense angiogenesis are a hallmark of many RCCs [8,9,10]. Recently, antiangiogenic drugs, such as tyrosine kinase inhibitors, have been approved for first-line therapy of RCC [11,12]. Because of these reasons, US assessment of blood flow may hold a significant potential not only for diagnostic purposes but also for monitoring therapy.…”

Evaluation of Acute Locoregional Toxicity in Patients with Breast Cancer Treated with Adjuvant Radiotherapy in Combination with Pazopanib

“…Vasudev and Larkin reported a phase III trial in which the most frequently reported AEs were diarrhea, hypertension, nausea, anorexia, and vomiting (5) [13]. The most common higher-grade toxicities (3/4) were hypertension (4%) and diarrhea (3%) (5) [13].…”

“…The most common higher-grade toxicities (3/4) were hypertension (4%) and diarrhea (3%) (5) [13]. Recent studies may indicate that the frequency of certain toxicities increase as the plasma concentration of pazopanib goes up (5) [13].…”

“…The most common higher-grade toxicities (3/4) were hypertension (4%) and diarrhea (3%) (5) [13]. Recent studies may indicate that the frequency of certain toxicities increase as the plasma concentration of pazopanib goes up (5) [13]. This was demonstrated in data for diarrhea and hypertension, but was not seen for fatigue, nausea, or vomiting (5) [13].…”

“…Recent studies may indicate that the frequency of certain toxicities increase as the plasma concentration of pazopanib goes up (5) [13]. This was demonstrated in data for diarrhea and hypertension, but was not seen for fatigue, nausea, or vomiting (5) [13]. This suggests that reducing dosages may be helpful in alleviating certain toxicities.…”