Cabozantinib

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Systematic (IUPAC) name
N-(4-((6,7-Dimethoxyquinolin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Clinical data
Trade names Cometriq
Licence data US FDA:link
Pregnancy cat. D (US)
Legal status ℞-only (US)
Routes Oral
Pharmacokinetic data
Protein binding ≥99.7%
Metabolism Hepatic (CYP3A4-mediated)
Half-life 55 hours
Excretion Faeces (54%), urine (27%)
Identifiers
CAS number 849217-68-1
ATC code None
ChemSpider 25948202
UNII 1C39JW444G
KEGG D10062
ChEBI CHEBI:72317 YesY
Synonyms XL184, BMS907351
Chemical data
Formula C28H24FN3O5 
Mol. mass 501.51 g mol

Cabozantinib (marketed under the tradename Cometriq, formerly known as XL184) is a small molecule inhibitor of the tyrosine kinases c-Met and VEGFR2, and has been shown to reduce tumor growth, metastasis, and angiogenesis.

It was developed by Exelixis Inc.

Cabozantinib was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011.[1]

Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer.[2] It is currently undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.

Approvals and indications

In October 2011, cabozantinib met its primary endpoint in a phase 3 clinical trial (EXAM) conducted by Exelixis investigating its effect on progression-free survival in medullary thyroid cancer.[3] A new drug application was submitted in the first half of 2012,[4] and on November 29, 2012 cabozantinib was granted marketing approval by the U.S. FDA under the name Cometriq for treating patients with medullary thyroid cancer.[2]

Grapefruit and grapefruit juice should be avoided as they may increase the concentration of the drug in the blood.[5]

It is not yet known if cabozantinib is safe and effective in children.

Clinical trials

In 2009 a phase II study for relapsed glioblastoma multiforme reported encouraging interim results.[6]

Positive data from clinical trials in 2011 indicate cabozantinib is beneficial in metastatic advanced prostate cancer (castration-resistant prostate cancer). 97% of patients either had stabilization or improvement in bone malignancies. The median time to disease progression was 29 weeks.[7][8]

One US trial reported in May 2011: The best results were seen in patients with liver, prostate, and ovarian cancer: 22 of 29 patients with liver cancer, 71 of 100 patients with prostate cancer, and 32 of 51 with ovarian cancer experienced either partial tumor shrinkage or stable disease. Fifty-nine out of 68 patients who had bone metastases had their metastases shrink or disappear during the trial.[9]

A pivotal trial for thyroid cancer should report interim results mid-2011.[7]

It is undergoing clinical trials for the treatment of prostate, ovarian, brain, melanoma, breast, non-small cell lung, hepatocellular and kidney cancers.[10]

See also

References

  1. ↑ Exelixis’ XL184 Granted Orphan Drug Designation and Assigned the Generic Name Cabozantinib. Jan 2011
  2. ↑ 2.0 2.1 "FDA approves Cometriq to treat rare type of thyroid cancer". 29 November 2012. 
  3. ↑ "Success for the EXAM trial". Retrieved 24 October 2011. 
  4. ↑ "Thyroid cancer drug cabozantinib prolongs PFS". Retrieved 24 October 2011. 
  5. ↑ "Cometriq prescribing information". Retrieved 29 November 2012. 
  6. ↑ "A phase II study of XL184 in patients (pts) with progressive glioblastoma multiforme (GBM) in first or second relapse.". 2009. 
  7. ↑ 7.0 7.1 "Exelixis drug slows prostate cancer spread in trial". Reuters. 6 June 2011. 
  8. ↑ Cabozantinib (XL184) Phase 2 Data Demonstrate Encouraging Clinical Activity in Patients with Castration-Resistant Prostate Cancer. Feb 2011
  9. ↑ "Cabozantinib Shrinks Tumors and Bone Metastases in Prostate and Other Cancers". 31 May 2011. 
  10. ↑ "Cabozantinib - List Results - ClinicalTrials.gov". U.S. National Institute of Health. Retrieved 25 April 2013. 

External links

Targeted therapy / extracellular chemotherapeutic agents/antineoplastic agents (L01)
CI monoclonal antibodies ("-mab")
Others for solid tumors
Tyrosine-kinase inhibitors ("-nib")

EML4-ALK (Crizotinib)

RET inhibitors: Vandetanib (Also VEGFR and EGFR).

c-MET inhibitor: Cabozantinib (Also VEGFR2).
Other

M: NEO

tsoc, mrkr

tumr, epon, para

drug (L1i/1e/V03)

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