Iwamoto Fabio M, Omuro Antonio M, Raizer Jeffrey J, Nolan Craig P, Hormigo Adília, Lassman Andrew B, Gavrilovic Igor T, Abrey Lauren E
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA.
J Neurooncol. 2008 Mar;87(1):85-90. doi: 10.1007/s11060-007-9491-3. Epub 2007 Nov 7.
To investigate the efficacy and safety of the combination of vinorelbine and intensive temozolomide for recurrent or progressive brain metastases from solid tumors.
Patients > or =18 years of age and with Karnofsky performance scale (KPS) > or = 60, adequate organ function and progressive or recurrent brain metastases were eligible. This was a phase II trial with 28-day cycles using temozolomide (150 mg/m(2), days 1-7 and 15-21) and vinorelbine 25 or 30 mg/m(2 )on days one and eight. The primary endpoint was objective radiographic response.
Thirty-eight patients (15 men, 23 women) with a median age of 57 years (range, 39-75) and median KPS of 80 were enrolled. The primary tumor sites were lung (n = 20), breast (n = 11), colorectal (n = 2), kidney (n = 2), bladder (n = 1), endometrium (n = 1), head and neck (n = 1). Prior therapies included chemotherapy (97%), whole-brain radiation therapy (79%), brain metastasis resection (53%) and stereotatic radiosurgery (47%). Objective radiographic response rate was 5% (one complete response and one minor response); five patients had stable disease, 29 progressive disease and two patients were not evaluable. Twenty-nine patients (76%) have died and the median follow-up of survivors was six months. Median progression-free and overall survivals were 1.9 and 5 months, respectively. Grade 3/4 toxicities were mainly hematological and two patients discontinued the study due to myelosuppression.
In this heavily pretreated population of patients with brain metastases, adding vinorelbine and increasing the intensity of temozolomide do not improve response rates compared to previous studies with single-agent temozolomide at standard doses.
探讨长春瑞滨联合强化替莫唑胺治疗实体瘤复发或进展性脑转移瘤的疗效和安全性。
年龄≥18岁、卡氏功能状态评分（KPS）≥60、器官功能良好且有进展性或复发性脑转移瘤的患者符合条件。这是一项II期试验，采用替莫唑胺（150mg/m²，第1 - 7天和第15 - 21天）和长春瑞滨25或30mg/m²，在第1天和第8天给药，每28天为一个周期。主要终点是影像学客观缓解。
共纳入38例患者（15例男性，23例女性），中位年龄57岁（范围39 - 75岁），中位KPS为80。原发肿瘤部位为肺（n = 20）、乳腺（n = 11）、结直肠（n = 2）、肾（n = 2）、膀胱（n = 1）、子宫内膜（n = 1）、头颈部（n = 1）。既往治疗包括化疗（97%）、全脑放疗（79%）、脑转移瘤切除术（53%）和立体定向放射外科治疗（47%）。影像学客观缓解率为5%（1例完全缓解和1例部分缓解）；5例患者疾病稳定，29例疾病进展，2例患者无法评估。29例患者（76%）死亡，幸存者的中位随访时间为6个月。中位无进展生存期和总生存期分别为1.9个月和5个月。3/4级毒性主要为血液学毒性，2例患者因骨髓抑制停止研究。
在这群接受过大量治疗的脑转移瘤患者中，与既往标准剂量单药替莫唑胺研究相比，加用长春瑞滨并增加替莫唑胺强度并未提高缓解率。
