Clinical and In vitro Studies of Imatinib in Advanced Carcinoid Tumors
Open Access
- 1 January 2007
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 13 (1), 234-240
- https://doi.org/10.1158/1078-0432.ccr-06-1618
Abstract
Purpose: Effective systemic therapy options for carcinoid tumors are lacking. We conducted in vitro studies and a phase II clinical trial to explore the activity of imatinib in carcinoid tumors. Experimental Design: Cells of the human bronchial carcinoid cell line NCI-H727 and the human pancreatic carcinoid cell line BON-1 were treated with increasing concentrations of imatinib using standard procedures to assess in vitro growth-inhibitory activity. A clinical trial using a two-stage phase II design to assess the response rate and safety profile of imatinib at a dose of 400 mg given twice daily in patients with advanced carcinoid tumors was completed. Results: In both cell lines, there was a dose- and time-dependent cytotoxic effect. The clinical trial enrolled 27 evaluable patients. Median duration on trial was 16 weeks. One patient had a partial response, 17 had stable disease, and 9 had progressive disease by the Response Evaluation Criteria in Solid Tumors criteria. Median progression-free survival time was 24 weeks. Median overall survival is 36 months. Seven patients who achieved a biochemical response had a superior progression-free survival time compared with patients without biochemical response (115 weeks compared with 24 weeks; P = 0.003). An increase in plasma basic fibroblast growth factor was associated with a shorter progression-free survival duration (P = 0.02). Conclusions: Our data suggest that imatinib is active in vitro and has a modest clinical activity in carcinoid patients. Changes in tumor markers may help select patients who are likely to benefit from therapy.Keywords
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