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Pazopanib
See also Imatinib
General information
Pazopanib is a potent, selective, broad-spectrum, multi-targeted inhibitor of receptor tyrosine kinases, including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-α/β, and c-kit. Total disease control in patients with advanced renal cell carcinoma was 82%. The most common adverse events included rises in aminotransferase activities, diarrhea, fatigue, nausea, hair depigmentation, and hypertension. According to an interim analysis, adverse reactions led to drug withdrawal in 5% of patients. Preliminary data suggested additional activity of the drug in ovarian cancer, with a comparable spectrum of adverse reactions [ ]. It has also been used in patients with recurrent glioblastoma [ ], cervical cancer [ ], breast cancer [ ], ovarian cancer [ ], thyroid cancer [ ], nasopharyngeal carcinoma [ ], and soft tissue sarcomas [ ].
Drug studies
Observational studies
In a study of the relation between serum cytokines and angiogenic factors (n = 85) and changes in soluble vascular endothelial growth factor receptor-2 (sVEGFR2) or placental-derived growth factor (PlGF) concentrations (n = 32), low interleukin (IL)-12 p40 subunit and MPC3 concentrations at baseline were associated with better progression-free survival at 12 weeks, low basic nerve growth factor and hepatocyte growth factor with a better progression-free survival, and low inter-cellular adhesion molecule-1 and IL-2 receptor alfa with prolonged overall survival [ ]. Pazopanib reduced sVEGFR2 and increased PlGF concentrations and low sVEGFR2 and high PlGF concentrations at week 12 were associated with higher-grade hypertension, with rises in TSH and with poorer progression-free survival and overall survival.
Organs and systems
Cardiovascular
In a systematic review of 13 clinical studies in 1651 patients with a variety of solid tumors the overall incidences of all-grade and high-grade hypertension were 36% (95% CI = 32, 41) and 6.5% (95% CI = 5.2, 8.0) respectively [ ]. Pazopanib was associated with an increased risk of all-grade hypertension (RR = 4.97, 95% CI = 3.38, 7.30) and high-grade hypertension (RR = 2.87, 95% CI = 1.16, 7.12). There was no significant difference in the incidence of all-grade hypertension (RR = 1.21; 95% CI = 0.96, 1.53) and high-grade hypertension (RR = 1.29; 95% = CI = 0.80, 2.07) between patients with and without renal cell carcinomas. The risk of all-grade hypertension with pazopanib was substantially higher than with sorafenib (RR = 1.99; 95% CI = 1.73, 2.29) and sunitinib (RR = 2.20; 95% CI = 1.92, 2.52), while the risk of pazopanib-induced high-grade hypertension was similar to the risk with sorafenib (RR = 0.98; 95% CI = 0.75, 1.30) and sunitinib (RR = 0.81; 95% CI = 0.62, 1.06).
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