Sunitinib in metastatic thymic carcinomas: laboratory findings and initial clinical experience.
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.
Ströbel
P
P
Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany. philipp.stroebel@umm.de
Bargou
R
R
Wolff
A
A
Spitzer
D
D
Manegold
C
C
Dimitrakopoulou-Strauss
A
A
Strauss
L
L
Sauer
C
C
Mayer
F
F
Hohenberger
P
P
Marx
A
A
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D000077210:Sunitinib; D013945:Thymoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013953:Thymus Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D020794:Receptor Protein-Tyrosine Kinases; D000077210:Sunitinib