NEUROONCOLOGY

神经肿瘤学

• 批准号: 6563773
• 负责人: JAN C BUCKNER
• 金额: $ 7.89万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-11 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563773
• 关键词: acridines; analog; anticonvulsants; antineoplastics; carboplatin; cisplatin; combination cancer therapy; cooperative study; drug interactions; gene therapy; glioma; human subject; human therapy evaluation; irinotecan; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; patient oriented research; pharmacokinetics; psychological aspect of cancer; sirolimus

The NCCTG Neuro-Oncology Program consists of three components: Cancer Treatment Trials, Neurobehavioral Studies, and Laboratory Correlates. These complementary components contribute to improving duration and quality of life in patients with primary central nervous system malignancies and to enhancing our understanding of the underlying disease process. During the previous grant cycle, in low-grade glioma patients, we observed that 65 cGy radiation is not better than 50 cGy; pro-carbazine, CCNU, grade glioma patients, we observed that 65 cGy radiation is not better than 50 cGy; procarbazine, CCNU, and vincristine (PCV) is an active regimen as initial therapy; and deletions in chromosomes 1p and 19q are associated with the diagnosis of low-grade oligodendrogliona, but not with low-grade oligoastrocytoma. In patients with high-grade glioma (glioblastoma multiforme, anaplastic oligoastrocytoma), we demonstrated that recombinant alpha interferon does not improve survival when added to radiation and BCNU, but is considerably more toxic; than grading (grade 3 versus grade 4) has significant prognostic value in patients with anaplastic oligoastrocytoma; and that, grade for grade, patients with anaplastic oligoastrocytoma have a statistically significant improved survival compared to those with pure astrocytoma. Moreover, tumoral EGFR amplification, absence of p53 mutations, and PTEN deletions are associated with poor survival in anaplastic astrocytoma patients. Glioblastoma and gliosarcoma patients have essentially identical clinical courses and genetic abnormalities. In recurrent glioma patients, we identified two active regimens: MOP (nitrogen mustard, vincristine, and procarbazine) and irinotecan. Ph. Pharmacokinetic studies demonstrated increase in CPT-11 clearance and variable metabolism in patients receiving irinotecal and anti-convulsants concurrently. Non-glioblastoma patients were more likely to respond to treatment than those with recurrent glioblastoma. Neurobehavioral studies indicated that good baseline Folstein and Folstein mini-mental status examination (MMSE) score is associated with better survival on multi-variate analyses. Few patients with high-grade glioma had diminished mini-mental examination scores at one year and 18 months in the absence of tumor progression. Conversely, reduction in mini-mental status examination scores correlated strongly with both at diagnosis, and were more likely to have cognitive decline to have cognitive decline as a consequence of treatment compared with younger patients. In patients with primary CNS lymphoma, we found a high response rate with CHOP (cyclophosphamide, doxorubicin, vincristine, and dexamethasone), but the duration of benefit was very short. As in patients with high-grade glioma, MMSE scores declined in close association with tumor progression. Future plans include continued evaluation of agents with radiosensitizing properties including cisplatin and irinotecan. We will continue to evaluate the efficacy of new regimens in recurrent glioma patients, including pyrazoloacridine plus carboplatin and the rapamycin analog, CCI 779. NCCTG has recruited investigators demonstrating experience with inhibitors of tumor invasion, as well as gene therapy. There are two main gene therapy approaches current in preclinical investigation: fusogenic membrane glycoproteins such as the measles virus F and H proteins and the truncated Gibbon Ape Leukemia virus surface protein (GALV). Neurobehavioral studies, including evaluation and treatment of impaired cognitive status, depression, fatigue, and excessive daytime somnolence, are in process. Pharmacokinetic studies to investigate interactions among chemotherapeutic agents and anti-convulsants will continue. Studies of genetic alterations in glioma, especially anaplastic astrocytoma and low- grade glioma, will be expanded through collaborations with Drs. Robert Jenkins (Mayo) David James (Mayo), and Bert Feuerstein (UCSF).

NCCTG神经肿瘤学计划包括三个组成部分：癌症治疗试验，神经行为研究和实验室相关性。这些互补成分有助于改善原发性中枢神经系统恶性肿瘤患者的持续时间和生活质量，并增强我们对潜在疾病过程的理解。在上一个赠款周期中，在低级神经胶质瘤患者中，我们观察到65个CGY辐射不高于50 CGY。前迦苯，CCNU，级别神经胶质瘤患者，我们观察到65个CGY辐射不高于50 CGY。 Procarbazine，CCNU和Vincristine（PCV）是一种活跃的方案，作为初始治疗。染色体1p和19q中的缺失与低度寡胶质细胞的诊断有关，但与低度寡构细胞瘤无关。在高级神经胶质瘤（多形胶质母细胞瘤，变性少聚细胞瘤）的患者中，我们证明重组α干扰素在添加到放射线和BCNU中并不能提高生存率，但毒性更大。比分级（3级与4级）具有显着的预后价值，在肿瘤性少细胞瘤患者中具有显着的预后价值。而且，与患有纯星形细胞瘤的患者相比，阶段性少细胞瘤患者的生存率提高了统计学意义。此外，肿瘤EGFR扩增，缺乏p53突变以及PTEN缺失与播种胶质细胞瘤患者的存活率差有关。胶质母细胞瘤和胶质肉瘤患者具有基本相同的临床课程和遗传异常。在复发性神经胶质瘤患者中，我们确定了两种活跃的方案：MOP（氮芥末，长春新碱和procarbazine）和Irinotecan。博士学位的药代动力学研究表明，同时接受虹膜和抗惊厥药的患者CPT-11清除率和可变代谢。与复发性胶质母细胞瘤相比，非糖母细胞瘤患者对治疗的反应更可能对治疗。神经行为研究表明，良好的基线Folstein和Folstein Mini-Mini-Menti-Menti-Inderal状态检查（MMSE）评分与多变量分析的更好生存有关。在没有肿瘤进展的情况下，很少有高级神经胶质瘤的患者在一年零18个月时降低了小精神检查评分。相反，小精神状态检查评分的降低与诊断时的两者都密切相关，并且与年轻患者相比，由于治疗的结果，认知能力下降更可能下降。在原发性中枢神经系统淋巴瘤的患者中，我们发现CHOP（环磷酰胺，阿霉素，长春新碱和地塞米松）的缓解率很高，但是收益持续时间很短。与高度神经胶质瘤患者一样，MMSE评分与肿瘤进展密切相关。未来的计划包括对具有放射敏感性的代理的继续评估，包括顺铂和伊立替康。我们将继续评估新方案在复发性神经胶质瘤患者中的功效，包括吡唑唑啶加上卡泊蛋白和雷帕霉素类似物，CCI779。NCCTG。NCCTG招募了研究人员，证明了研究人员，证明了具有肿瘤抑制剂的经验，以及基因治疗。临床前研究中有两种主要的基因治疗方法：融合膜糖蛋白，例如麻疹病毒F和H蛋白以及截短的长臂猿白血病病毒表面蛋白（GALV）。神经行为研究，包括对认知状况受损，抑郁，疲劳和白天过度迟感的评估和治疗，正在进行过程中。研究化学治疗剂和抗惊厥药之间相互作用的药代动力学研究将继续进行。神经胶质瘤的遗传改变，尤其是型间变性星形细胞瘤和低级神经胶质瘤的研究，将通过与DRS的合作进行扩展。罗伯特·詹金斯（Mayo）David James（Mayo）和Bert Feuerstein（UCSF）。