Ekeblad Sara, Sundin Anders, Janson Eva Tiensuu, Welin Staffan, Granberg Dan, Kindmark Henrik, Dunder Kristina, Kozlovacki Gordana, Orlefors Håkan, Sigurd Mattias, Oberg Kjell, Eriksson Barbro, Skogseid Britt
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Clin Cancer Res. 2007 May 15;13(10):2986-91. doi: 10.1158/1078-0432.CCR-06-2053.
A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors.
Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m(2)) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O(6)-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n=23) and compared with response to temozolomide.
Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O(6)-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses.
Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
对替莫唑胺治疗晚期神经内分泌肿瘤的毒性和疗效进行回顾性分析。
36例晚期神经内分泌肿瘤患者（1例胃神经内分泌肿瘤、7例胸腺神经内分泌肿瘤、13例支气管类癌、12例胰腺内分泌肿瘤、1例副神经节瘤、1例神经内分泌前肠肿瘤和1例神经内分泌盲肠癌）接受替莫唑胺（200 mg/m²）治疗，每4周给药5天。患者此前平均接受过2.4种抗肿瘤治疗方案。根据实体瘤疗效评价标准，每3个月对患者进行一次意向性放射学评估，以评估肿瘤反应。同时还评估了循环肿瘤标志物血浆嗜铬粒蛋白A。通过免疫组织化学方法研究了与化疗耐药相关的O⁶-甲基鸟嘌呤-DNA甲基转移酶的表达（n = 23），并将其与替莫唑胺的反应进行比较。
中位总疾病进展时间为7个月（95%置信区间，3 - 10）。14%的患者出现放射学反应，53%的患者疾病稳定。副作用主要为血液学方面；14%的患者出现3级或4级血小板减少（美国国立癌症研究所毒性标准）。10例患者肿瘤的O⁶-甲基鸟嘌呤-DNA甲基转移酶免疫反应性在<10%的细胞核中，而4例患者出现放射学反应。
在一小部分晚期恶性神经内分泌肿瘤患者中，替莫唑胺单药治疗具有可接受的毒性和抗肿瘤作用，其中4例出现放射学反应。
