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Axitinib: Treatment of Advanced Renal Cell Cancer
Mechanism of Action of Axitinib
Axitinib is an oral potent inhibitor of VEGF receptor tyrosine kinases 1–3, which thus inhibits the intracellular signal transduction of cell growth, angiogenesis and promotes apoptosis of tumor cells.
Urological Indications for Axitinib
Axitinib is approved for the treatment of metastatic renal cell carcinoma after previous failure of treatment with sunitinib or a cytokine (immunotherapy). Axitinib demonstrated in a randomized comparison with sorafenib an improved progression-free survival (6.7 vs. 4.7 months), this was particularly significant in patients with failure of immunotherapy (Rini et al., 2011).
Pharmacokinetics of Axitinib
Oral administration of axitinib. Hepatic metabolism. Half-life time is 2.5 to 6 h.
Side Effects of Axitinib
The most common side effects (> 20%) are diarrhea, hypertension, fatigue, dysphonia, nausea, decreased appetite, and hand-foot syndrome. For the following side effects, the incidences of grade 3/4 adverse events are specified in parentheses.
Diarrhea (10%), vomiting (1–2%).
Hand-foot syndrome (5%), mucositis (1–2%).
Hypertension (15%), arterial or venous embolism (2–3%).
Other side effects:
Hypothyroidism, lack of appetite (3%), dehydration (2–3%), fatigue (10%).
Interactions with Axitinib
No concomitant medication of axitinib with strong inhibitors of CYP3A4/5 like macrolide antibiotics or ketoconazole.
Contraindications of Axitinib
- Axitinib is contraindicated if there are persistent side effects grade 3 and 4 despite dose reduction.
- Severe hepatic insufficiency (Child C)
- Pregnancy and lactation
Dosage of Axitinib
Axitinib is started with 5 mg 1-0-1 per os continuously. The dose is increased to 7 mg and 10 mg 1-0-1, if possible. If relevant adverse effects are present, the dosage is reduced to 7 mg 1-0-1, 5 mg 1-0-1, 3 mg 1-0-1 and then 2 mg 1-0-1, the alternative is a pause of medication.
Clinical Controls During Therapy:
Regular checks of blood count, electrolytes, liver function tests, clotting tests, blood sugar, creatinine, thyroid hormones. Regular examination of the skin, oral cavity, and blood pressure.
Counter diarrhea with loperamide, prevent mucositis with regular mouthwashes, prevent hand-foot skin reaction with avoidance of mechanical load or if necessary with keratolytic or steroid ointments, treat hypertension with antihypertensive drugs, replace thyroid hormones in hypothyroidism. Without improvement of adverse effects, dose reduction or a pause of medication is necessary.
Brand Names of Axitinib:
Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
ReferencesRini, B. I.; Escudier, B.; Tomczak, P.; Kaprin, A.; Szczylik, C.; Hutson, T. E.; Michaelson, M. D.; Gorbunova, V. A.; Gore, M. E.; Rusakov, I. G.; Negrier, S.; Ou, Y.; Castellano, D.; Lim, H. Y.; Uemura, H.; Tarazi, J.; Cella, D.; Chen, C.; Rosbrook, B.; Kim, S. & Motzer, R. J. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial.
Lancet, 2011, 378, 1931-1939.
Deutsche Version: Axitinib