Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience

Br J Cancer. 2010 Jul 13;103(2):196-200. doi: 10.1038/sj.bjc.6605740. Epub 2010 Jun 22.

Abstract

Background: Thymic carcinoma (TC) is a rare aggressive tumour. Median survival with current treatments is only 2 years. Sunitinib is a multi-targeted tyrosine kinase inhibitor that has shown benefit in various other cancers.

Methods: Laboratory analyses of snap-frozen tumour tissues were performed to detect activation and genetic mutations of receptor tyrosine kinases (RTKs) in TC samples. On the basis of molecular analyses showing activation of multiple RTKs in their tumour, four patients with metastatic TCs refractory to conventional therapies were treated with sunitinib according to standard protocols.

Results: RTK analysis in three of the patients showed activation of multiple RTKs, including platelet-derived growth factor-beta and vascular endothelial growth factor 3. Mutations of EGFR, c-KIT, KRAS, and BRAF genes were not found. Administration of sunitinib yielded a partial remission (lasting 2 to 18+ months) according to the RECIST criteria in three patients and stable disease with excellent metabolic response in 18F-FDG-PET in another one. The overall survival with sunitinib treatment ranges from 4 to 40+ months. Withdrawal of the drug in one patient prompted rapid tumour progression that could be controlled by re-administration of sunitinib.

Conclusions: Sunitinib is an active treatment for metastatic TC. A panel of molecular analyses may be warranted for optimal patient selection.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Male
  • Mutation
  • Neoplasm Metastasis
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Sunitinib
  • Thymoma / drug therapy*
  • Thymoma / enzymology
  • Thymoma / pathology
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / enzymology
  • Thymus Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Receptor Protein-Tyrosine Kinases
  • Sunitinib