Sunitinib Possible Sex-Divergent Therapeutic Outcomes.
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.
Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avn. Joan XXIII, s/n, Barcelona, 08028, Spain. segarra100@gmail.com.
Ignacio
http://orcid.org/0000-0002-8721-2393
I
Segarra
Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avn. Joan XXIII, s/n, Barcelona, 08028, Spain.
Pilar
P
Modamio
Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avn. Joan XXIII, s/n, Barcelona, 08028, Spain.
Cecilia
C
Fernández
Clinical Pharmacy and Pharmacotherapy Unit, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Avn. Joan XXIII, s/n, Barcelona, 08028, Spain.
Eduardo L
EL
Mariño
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib