Ahluwalia Manmeet S, Xie Hao, Dahiya Saurabh, Hashemi-Sadraei Nooshin, Schiff David, Fisher Paul G, Chamberlain Marc C, Pannullo Susan, Newton Herbert B, Brewer Cathy, Wood Laura, Prayson Richard, Elson Paul, Peereboom David M
Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue (S70), Cleveland, OH, 44195, USA.
J Neurooncol. 2015 Mar;122(1):111-9. doi: 10.1007/s11060-014-1684-y. Epub 2014 Dec 23.
Standard initial therapy for patients with pure and mixed anaplastic oligodendrogliomas (AO/MAO) includes chemotherapy and radiation therapy. Anaplastic oligodendrogliomas with 1p/19q co-deletion are more responsive to chemotherapy. There is concern for potential long-term CNS toxicity of radiation. Hence an approach using chemotherapy initially and reserving radiation for progressive disease is attractive. This multicenter phase II trial included patients with newly diagnosed AO/MAO with central pathology review and 1p/19q assay. Temozolomide was given 150 mg/m(2) days 1-7 and 15-21, every 28 days for 8 cycles. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate, overall survival (OS), treatment toxicity and health-related quality of life (HRQL). Data from 62 patients enrolled between December 2001 and April 2007 at seven centers were analyzed. Among patients with measurable disease, 8 % achieved complete remission, 56 % had stable disease and 36 % had progression. The median PFS and OS were 27.2 months (95 % CI 11.9-36.3) and 105.8 months (95 % CI 51.5-N/A), respectively. Both 1p loss and 1p/19q co-deletion were positive prognostic factors for PFS (p < 0.001) and OS (p < 0.001); and there was some suggestion that 1p/19q co-deletion also predicted better response to chemotherapy (p = 0.007). Grade 3/4 toxicities were mainly hematological. Significantly improved HRQL in the future uncertainty domain of the brain cancer module was seen after cycle 4 (p < 0.001). This trial achieved outcomes similar to those reported previously. Toxicities from dose-intense temozolomide were manageable. Improvement in at least one HRQL domain increased over time. This trial supports the further study of first-line temozolomide monotherapy as an alternative to radiation therapy for patients with newly diagnosed AO/MAO with 1p 19q co-deleted tumors.
纯性和混合性间变性少突胶质细胞瘤（AO/MAO）患者的标准初始治疗包括化疗和放射治疗。1p/19q共缺失的间变性少突胶质细胞瘤对化疗更敏感。人们担心放疗可能存在潜在的长期中枢神经系统毒性。因此，一种先使用化疗，将放疗留待疾病进展时使用的方法很有吸引力。这项多中心II期试验纳入了新诊断的AO/MAO患者，进行了中心病理学评估和1p/19q检测。替莫唑胺在第1 - 7天和第15 - 21天给予150 mg/m²，每28天为一个周期，共8个周期。主要终点是无进展生存期（PFS）。次要终点包括缓解率、总生存期（OS）、治疗毒性和健康相关生活质量（HRQL）。分析了2001年12月至2007年4月在7个中心入组的62例患者的数据。在可测量疾病的患者中，8%达到完全缓解，56%疾病稳定，36%疾病进展。PFS和OS的中位数分别为27.2个月（95%CI 11.9 - 36.3）和105.8个月（95%CI 51.5 - N/A）。1p缺失和1p/19q共缺失都是PFS（p < 0.001）和OS（p < 0.001）的阳性预后因素；并且有一些迹象表明1p/19q共缺失也预示对化疗反应更好（p = 0.007）。3/4级毒性主要是血液学毒性。第4周期后，在脑癌模块的未来不确定性领域中，HRQL有显著改善（p < 0.001）。该试验取得了与先前报道相似的结果。高强度替莫唑胺的毒性是可控的。随着时间推移，至少一个HRQL领域的改善有所增加。该试验支持进一步研究一线替莫唑胺单药治疗作为新诊断的1p 19q共缺失肿瘤的AO/MAO患者放射治疗的替代方案。
