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Clinical and In vitro Studies of Imatinib in Advanced Carcinoid Tumors

Authors' Affiliation: Departments of Gastrointestinal Medical Oncology, Pathology, Internal Medicine, Diagnostic Imaging, Biostatistics and Applied Mathematics, and Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: James C. Yao, Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M.D. Anderson Cancer, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-2828; Fax: 713-563-0539; E-mail: jyao{at}mdanderson.org.

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.

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