The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R

David J. Gross*, Gabriel Munter, Menachem Bitan, Tali Siegal, Alberto Gabizon, Ronny Weitzen, Ofer Merimsky, Aliza Ackerstein, Asher Salmon, Avishai Sella, Shimon Slavin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC - disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC - disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo - disease progression in 2 patients; Carcinoid - stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET - disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.

Original languageEnglish
Pages (from-to)535-540
Number of pages6
JournalEndocrine-Related Cancer
Volume13
Issue number2
DOIs
StatePublished - Jun 2006
Externally publishedYes

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