Clinical and Preclinical Experience with Gefitinib and Sunitinib

Abstract

Gefitinib and sunitinib are new targeted agents in cancer therapy. As a single-target agent gefitinib was one of the first tyrosine kinase inhibitors in solid cancers. It is an inhibitor of the intracellular domain of the epidermal growth factor receptor (EGFR). Most experience with this drug was made in the treatment of non-small cell lung cancer. Its efficacy in most other solid cancers is limited. Several studies could show an association between the response of non-small cell lung cancers to gefitinib and a mutation of the EGFR gene. This mutation changes the target and alters the sensitivity for the drug. In breast cancer limited data of phase II studies showed response rates lower than 2%. Sunitinib as a multitarget agent inhibits several targets like vascular epidermal growth factor receptors (VEGFR) and other receptor tyrosine kinases. The efficacy of sunitinib against tumors is attributable to a direct antitumor activity and to an inhibition of neoangiogenesis. Most data exist for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Sunitinib could clearly improve the systemic treatment of these diseases. In the treatment of metastatic breast cancer response rates for the single agent therapy of 11% could be reported, which made this agent interesting for further phase III studies. These phase III studies are currently ongoing.

Challenges in the Development of Novel Targeted Therapies

“…The articles of Untch and Jackisch [4], Schuetz et.al. [5], Fasching et al [6], and Jackisch and Untch [7] demonstrate that the discovery and validation of mechanism-based biomarkers and the selection of the appropriate subset of patients in which the biomarker has functional relevance will be integral to the successful development of novel targeted agents in breast cancer. Moreover, their articles clearly emphasize that the translation of molecular insights into useful therapeutic approaches is highly complex, and the success of any particular approach is by no means guaranteed.…”