Sunitinib Possible Sex-Divergent Therapeutic Outcomes.
Ignacio SegarraPilar ModamioCecilia FernándezEduardo L MariñoPublished in: Clinical drug investigation (2017)
Sunitinib is a tyrosine kinase inhibitor used for the treatment of renal cell carcinoma and metastatic brain tumors. Preclinical pharmacokinetic studies have shown higher sunitinib hepatic and brain exposure in female mice and higher sunitinib kidney concentrations in male mice. We explored whether sex-divergent tissue pharmacokinetics may anticipate sex-divergent therapeutic and toxicology responses in male and female patients. The review of the available scientific literature identified case reports, case series reports, clinical trials, and other studies associating sex with sunitinib outcomes. The results suggest male patients may respond better to renal cell carcinoma treatment and female patients may have better brain tumor treatment outcomes but a higher incidence of adverse events. Although more high-quality evidence is needed, these results, as anticipated by the preclinical data, may indicate possible sunitinib sex-divergent therapeutic outcomes in patients. In addition, we propose the systematic analysis of sex-based outcomes in clinical trial reports and their inclusion and review in the ethics committees and review boards to prevent, amongst others, patient burden in upcoming clinical trials.
Keyphrases
- white matter
- multiple sclerosis
- renal cell carcinoma
- clinical trial
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- peritoneal dialysis
- public health
- squamous cell carcinoma
- systematic review
- type diabetes
- mesenchymal stem cells
- emergency department
- metastatic renal cell carcinoma
- subarachnoid hemorrhage
- skeletal muscle
- blood brain barrier
- big data
- functional connectivity
- phase iii
- cerebral ischemia