Yao James C, Zhang Jun X, Rashid Asif, Yeung Sai-Ching J, Szklaruk Janio, Hess Kenneth, Xie Keping, Ellis Lee, Abbruzzese James L, Ajani Jaffer A
Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2007 Jan 1;13(1):234-40. doi: 10.1158/1078-0432.CCR-06-1618.
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.
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.
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).
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.
类癌肿瘤缺乏有效的全身治疗方案。我们进行了体外研究和一项II期临床试验，以探索伊马替尼在类癌肿瘤中的活性。
使用标准程序，用递增浓度的伊马替尼处理人支气管类癌细胞系NCI-H727和人胰腺类癌细胞系BON-1的细胞，以评估体外生长抑制活性。完成了一项采用两阶段II期设计的临床试验，以评估伊马替尼对晚期类癌肿瘤患者每日两次、每次400 mg剂量给药时的缓解率和安全性。
在两种细胞系中，均存在剂量和时间依赖性细胞毒性作用。该临床试验纳入了27例可评估患者。试验的中位持续时间为16周。根据实体瘤疗效评价标准，1例患者部分缓解，17例病情稳定，9例病情进展。中位无进展生存时间为24周。中位总生存期为36个月。与无生化反应的患者相比，7例出现生化反应的患者无进展生存时间更长（分别为115周和24周；P = 0.003）。血浆碱性成纤维细胞生长因子升高与无进展生存期缩短相关（P = 0.02）。
我们的数据表明，伊马替尼在体外具有活性，在类癌患者中具有适度的临床活性。肿瘤标志物的变化可能有助于选择可能从治疗中获益的患者。
