Congress Abstracts 2006

45

SAFETY PERSPECTIVES ON THE ROLE OF AMG 706, AN INVESTIGATIONAL, ORAL, MULTIKINASE INHIBITOR (MKI), FOR SECOND-LINE TREATMENT OF GASTROINTESTINAL STROMAL TUMORS (GIST). Marilyn Mulay, RN, MS, OCN^®, Premiere Oncology, Santa Monica, CA.

Multikinase inhibitors (MKIs) are being examined for the treatment of gastrointestinal stromal tumors (GIST), a rare neoplasm characterized by well-defined mutations in growth factor receptors (incidence estimated at 5000 cases per year in the US). Patients with GIST frequently possess mutations in c-KIT, which encodes for a receptor tyrosine kinase involved in tumor cell proliferation. Imatinib, a small molecule cancer therapeutic, inhibits Kit and is currently approved for the treatment of GIST. Many imatinib-treated patients with GIST relapse due to additional mutations that confer imatinib resistance. Therefore, new therapeutics targeting mutant Kit and other oncogenic pathways are needed. Angiogenesis, the formation of blood vessels from the existing vasculature, is involved in the malignant potential of GIST. Inhibitors of angiogenesis are important therapeutic candidates for the treatment of imatinib-resistant GIST.

To provide a fundamental introduction to GIST and the side effects seen with AMG 706 treatment, along with methods for managing them.

AMG 706 is an oral MKI that inhibits vascular endothelial growth factor receptors (VEGFR), Kit, and platelet-derived growth factor receptors (PDGFR), resulting in potent inhibition in models of angiogenesis, tumor proliferation, and lymphangiogenesis. AMG 706 inhibits tumor growth directly and blocks its blood supply. AMG 706 is being examined in patients with imatinib-resistant GIST.

Side effects of AMG 706 most commonly include hypertension, diarrhea, fatigue, nausea, and headache. Hypertension has been observed with other antiangiogenic agents and is easily manageable with antihypertensive medication. Patients treated with AMG 706 should be frequently monitored for blood pressure changes. Antihypertensive drugs may be prescribed to bring blood pressure to acceptable levels. The short half-life of AMG 706 allows for rapid treatment interruption in the case of serious adverse effects.

AMG 706 is generally well tolerated, and its activity on multiple kinase targets, including VEGFR, PDGFR, and possibly mutant Kit, makes it an ideal candidate for imatinib-resistant GIST. The side effects of AMG 706 tend to be related to its antiangiogenic activity, and are easily monitored and managed.