Sunitinib in the management of gastrointestinal stromal tumours (GISTs)

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the gut with a 5-year survival of approximately 50%. Surgery remains the treatment of choice in resectable disease, with conventional chemotherapy largely ineffective. Over 90% of GIST possesses mutations in the c-KIT oncogene, producing an overactive tyrosine kinase, which may be driving the malignant process. Imatinib inhibits the aberrant tyrosine kinase and imatinib therapy in metastatic disease has shown significant clinical benefit. However, resistance typically develops within 2 years, with the need for further therapy. This article aims to introduce the reader to a new development in cancer therapeutics.

A literature search was performed using the MEDLINE database to identify publications relevant to the review. References within these articles were used to expand the search. Abstracts from recent ASCO symposia were hand searched for relevant articles.

Sunitinib (SU11248) is a novel multi-targeted tyrosine kinase inhibitor with activity not only against the receptor tyrosine kinase product of c-KIT but also other cell-signalling pathways that may be relevant in GIST; FLT3, platelet-derived growth receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). Two Phase II trials and one Phase III trial have investigated the activity of sunitinib against imatinib-resistant GIST. Early results showed significant benefits in time to disease progression that led to licensing of the drug in America and more recently in Europe. A Phase III trial comparing dose-increased imatinib and sunitinib in progressed GIST is currently planned.

Initial clinical results with sunitinib are promising and suggest a future role. Further studies are needed before sunitinib can be recommended for the routine treatment of imatinib-refractory GIST.