The value of temozolomide in combination with radiotherapy during standard treatment for newly diagnosed glioblastoma

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• 作者：Chul-Kee Park (1)
  Se-Hoon Lee (2) (6)
  Tae Min Kim (2) (6)
  Seung Hong Choi (3)
  Sung-Hye Park (4)
  Dae Seog Heo (2) (6)
  Il Han Kim (5)
  Hee-Won Jung (1)
  
• 关键词：Glioblastoma ; Temozolomide ; Concomitant ; Adjuvant ; MGMT
• 刊名：Journal of Neuro-Oncology
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：112
• 期：2
• 页码：277-283
• 全文大小：321KB
• 参考文献：1. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987-96 CrossRef
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  4. Lanzetta G, Campanella C, Rozzi A et al (2003) Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Anticancer res 23:5159-164
  5. Stupp R, Dietrich PY, Ostermann Kraljevic S et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol: Off J Am Soc Clin Oncol 20:1375-382 CrossRef
  6. Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459-66 CrossRef
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  8. Kim IH, Park CK, Heo DS et al (2011) Radiotherapy followed by adjuvant temozolomide with or without neoadjuvant ACNU-CDDP chemotherapy in newly diagnosed glioblastomas: a prospective randomized controlled multicenter phase III trial. J Neurooncol 103:595-02 CrossRef
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  11. Park CK, Kim J, Yim SY et al (2011) Usefulness of MS-MLPA for detection of MGMT promoter methylation in the evaluation of pseudoprogression in glioblastoma patients. Neuro-oncology 13:195-02 CrossRef
  12. Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997-003 CrossRef
  13. Chakravarti A, Erkkinen MG, Nestler U et al (2006) Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms. Clin Cancer Res 12:4738-746 CrossRef
  14. Koukourakis GV, Kouloulias V, Zacharias G et al (2009) Temozolomide with radiation therapy in high grade brain gliomas: pharmaceuticals considerations and efficacy; a review article. Molecules 14:1561-577 CrossRef
  15. Kil WJ, Cerna D, Burgan WE et al (2008) In vitro and in vivo radiosensitization induced by the DNA methylating agent temozolomide. Clin Cancer Res 14:931-38 CrossRef
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• 作者单位：Chul-Kee Park (1)
  Se-Hoon Lee (2) (6)
  Tae Min Kim (2) (6)
  Seung Hong Choi (3)
  Sung-Hye Park (4)
  Dae Seog Heo (2) (6)
  Il Han Kim (5)
  Hee-Won Jung (1)
  
  1. Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea
  6. Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
  3. Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
  4. Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
  5. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
  
• ISSN：1573-7373

文摘

The current best standard care for glioblastoma still has limitations and unsatisfactory outcomes in patients with an unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Whether the effects of temozolomide are primarily due to its concomitant use with radiotherapy or are also mediated by their independent use in the adjuvant phase remain unclear. To validate the concomitant use of temozolomide in the standard protocol, we compared the overall survival of two prospective patient groups: one treated with radiotherapy alone followed by adjuvant temozolomide (RT?→?TMZ group) and the other treated with concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (CCRT-TMZ group). Each patient in the RT?→?TMZ group (n?=?25) was matched with two patients in the CCRT-TMZ group (n?=?50) with respect to age, extent of resection, MGMT promoter methylation status, and postsurgical performance status to minimize the influence of confounding factors. In patients with MGMT promoter methylation, the CCRT-TMZ group showed superior overall survival (OS; median, 41.0?months) and progression-free survival (PFS; median, 24.0?months) compared with the RT?→?TMZ group. However, the OS and PFS did not differ between the CCRT-TMZ and the RT?→?TMZ groups in the patients without MGMT promoter methylation. Although this data is from a retrospective analysis using small number of patients, the study might indicate that concomitant use of temozolomide with radiotherapy is a crucial step in the standard treatment for glioblastoma patients with MGMT promoter methylation. And the use of temozolomide, either concurrently or by adjuvant after radiotherapy, remains a questionable value for those with an unmethylated MGMT promoter.