Giorgio Carmelo Giannitto, Giuffrida Dario, Pappalardo Alessandro, Russo Antonio, Santini Daniele, Salice Placida, Blanco Giusy, Castorina Sergio, Failla Giuseppe, Bordonaro Roberto
Gravina Hospital, Oncology Unit, Caltagirone, Italy.
Lung Cancer. 2005 Nov;50(2):247-54. doi: 10.1016/j.lungcan.2005.05.026. Epub 2005 Jul 20.
The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease.
Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment.
Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity.
The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy.
最有可能转移至脑部的原发性肿瘤类型是肺癌。在经过大量前期治疗的患者中，可用的治疗选择有限，且文献报道的现有治疗方法的结果令人失望。本II期研究旨在评估替莫唑胺（TMZ）作为非小细胞肺癌（NSCLC）患者脑转移瘤（BrM）姑息治疗的疗效和安全性，这些患者之前接受过全脑放疗（WBRT）以及至少一线针对转移性脑疾病的化疗。
替莫唑胺首个周期连续5天口服给药，剂量为150mg/m²/天，若未观察到3/4级血液学毒性，后续周期每28天剂量增加至200mg/m²/天，持续5天。入选标准包括经细胞学或组织学确诊的NSCLC；脑转移瘤，在接受WBRT和至少一线化疗后复发或进展。共有30例连续患者进入研究并接受分配的治疗。
3例患者（10%）脑转移瘤达到客观缓解（OR），其中2例完全缓解。3例（10%）患者病情稳定，24例（80%）患者病情进展。据报道，对替莫唑胺的反应与对之前一线化疗的敏感性之间存在相关性。对缓解患者和所有纳入患者均检查了疾病进展时间和总生存期。对于长期存活者，我们考虑在开始使用替莫唑胺后存活超过12个月的患者。根据此定义，3例患者为长期存活者：2例达到客观缓解，1例脑疾病稳定。未发生3级或4级毒性。治疗相关不良事件总体为轻度或中度（1-2级）。没有患者因治疗相关毒性而停用替莫唑胺。
本试验结果清楚地表明，替莫唑胺在先前接受过WBRT和至少一线化疗的NSCLC脑转移瘤患者中具有活性且安全。
