Cabozantinib (XL184) for the treatment of locally advanced or metastatic progressive medullary thyroid cancer

David Viola; Virginia Cappagli; Rossella Elisei

doi:10.2217/fon.13.128

Cabozantinib (XL184) for the treatment of locally advanced or metastatic progressive medullary thyroid cancer

Future Oncol. 2013 Aug;9(8):1083-92. doi: 10.2217/fon.13.128.

Authors

David Viola¹, Virginia Cappagli, Rossella Elisei

Affiliation

¹ Endocrinology Unit, Department of Clinical & Experimental Medicine, WHO Collaborating Center for the Study & Treatment of Thyroid Diseases & other Endocrine & Metabolic Disorders, University of Pisa, Via Paradisa 2, Pisa 56124, Italy.

PMID: 23902240
DOI: 10.2217/fon.13.128

Abstract

Cabozantinib (XL184) is an oral multiple receptor tyrosine kinase inhibitor manufactured by Exelixis Inc., CA, USA. It mainly inhibits three tyrosine kinase receptors: MET, VEGFR2 and RET. In both preclinical and clinical studies it has been shown to inhibit tumor angiogenesis, invasiveness and metastases. The most frequent side effects are fatigue, diarrhea, decreased appetite, nausea, weight loss and palmar-plantar erythrodysesthesia. A Phase III clinical trial (EXAM study) of XL184 versus placebo in advanced and progressive medullary thyroid cancer showed a 28 versus 0% overall response rate and a progression-free survival of 11.2 versus 4.0 months (hazard ratio: 0.28; 95% CI: 0.19-0.40; p < 0.0001) in patients treated with cabozantinib and placebo, respectively. The drug has been approved by the US FDA for the treatment of advanced/progressive metastatic medullary thyroid cancer in the USA. The EMA is now evaluating its approval in Europe.

Publication types

Evaluation Study

MeSH terms

Anilides / administration & dosage*
Anilides / adverse effects
Anilides / pharmacokinetics
Carcinoma, Neuroendocrine
Clinical Trials, Phase III as Topic
Drug Approval
Drug-Related Side Effects and Adverse Reactions / chemically induced
Drug-Related Side Effects and Adverse Reactions / classification
Drug-Related Side Effects and Adverse Reactions / pathology
Humans
Neoplasm Invasiveness / pathology
Neoplasm Invasiveness / prevention & control
Neoplasm Metastasis / drug therapy*
Neoplasm Metastasis / pathology
Neoplasm Recurrence, Local / drug therapy
Neoplasm Recurrence, Local / pathology
Neovascularization, Pathologic / drug therapy
Protein Kinase Inhibitors / administration & dosage*
Protein Kinase Inhibitors / adverse effects
Protein Kinase Inhibitors / pharmacokinetics
Pyridines / administration & dosage*
Pyridines / adverse effects
Pyridines / pharmacokinetics
Thyroid Neoplasms / drug therapy*
Thyroid Neoplasms / pathology

Substances

Anilides
Protein Kinase Inhibitors
Pyridines
cabozantinib

Supplementary concepts

Thyroid cancer, medullary