This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Quinn, J. A. Articles by Friedman, H. S. Search for Related Content PubMed PubMed Citation Articles by Quinn, J. A. Articles by Friedman, H. S. Social Bookmarking                            What's this?

Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma

From the Departments of Surgery, Radiology, Pathology, Biostatistics and Bioinformatics (JH), Duke University Medical Center, Durham, NC; Hassenfeld Cancer Center, and Beth Israel Medical Center, New York, NY; Walt Disney Memorial Cancer Institute, Orlando, FL; and Schering-Plough Research Institute, Kenilworth, NJ.

Address reprint requests to Jennifer A. Quinn, MD, The Brain Tumor Center at Duke, Box 3624 Duke University Medical Center, Durham, NC 27710; email: quinn008{at}mc.duke.edu.

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma.

Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m²/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity.

Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death.

Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				Y. Sawamura, Y. Kamoshima, T. Kato, T. Tajima, and J. Tsubaki Chemotherapy with Cisplatin and Vincristine for Optic Pathway/Hypothalamic Astrocytoma in Young Children Jpn. J. Clin. Oncol., May 1, 2009; 39(5): 277 - 283. [Abstract] [Full Text] [PDF]

				S. Kesari, D. Schiff, J. Drappatz, D. LaFrankie, L. Doherty, E. A. Macklin, A. Muzikansky, S. Santagata, K. L. Ligon, A. D. Norden, et al. Phase II Study of Protracted Daily Temozolomide for Low-Grade Gliomas in Adults Clin. Cancer Res., January 1, 2009; 15(1): 330 - 337. [Abstract] [Full Text] [PDF]

				J. A. Maxwell, S. P. Johnson, R. E. McLendon, D. W. Lister, K. S. Horne, A. Rasheed, J. A. Quinn, F. Ali-Osman, A. H. Friedman, P. L. Modrich, et al. Mismatch Repair Deficiency Does Not Mediate Clinical Resistance to Temozolomide in Malignant Glioma Clin. Cancer Res., August 1, 2008; 14(15): 4859 - 4868. [Abstract] [Full Text] [PDF]

				J. C. Buckner, P. D. Brown, B. P. O'Neill, F. B. Meyer, C. J. Wetmore, and J. H. Uhm Central Nervous System Tumors Mayo Clin. Proc., October 1, 2007; 82(10): 1271 - 1286. [Abstract] [Full Text] [PDF]

				D. Schiff, P. D. Brown, and C. Giannini Outcome in adult low-grade glioma: The impact of prognostic factors and treatment Neurology, September 25, 2007; 69(13): 1366 - 1373. [Abstract] [Full Text] [PDF]

				P. Y. Wen and L. M. DeAngelis Chemotherapy for low-grade gliomas: Emerging consensus on its benefits Neurology, May 22, 2007; 68(21): 1762 - 1763. [Full Text] [PDF]

				G. Kaloshi, A. Benouaich-Amiel, F. Diakite, S. Taillibert, J. Lejeune, F. Laigle-Donadey, M.-A Renard, W. Iraqi, A. Idbaih, S. Paris, et al. Temozolomide for low-grade gliomas: Predictive impact of 1p/19q loss on response and outcome Neurology, May 22, 2007; 68(21): 1831 - 1836. [Abstract] [Full Text] [PDF]

				S. Gururangan, M. J. Fisher, J. C. Allen, J. E. Herndon II, J. A. Quinn, D. A. Reardon, J. J. Vredenburgh, A. Desjardins, P. C. Phillips, M. A. Watral, et al. Temozolomide in Children with progressive low-grade glioma Neuro-oncol, April 1, 2007; 9(2): 161 - 168. [Abstract] [Full Text] [PDF]

				J. T. Grier and T. Batchelor Low-grade gliomas in adults. Oncologist, June 1, 2006; 11(6): 681 - 693. [Abstract] [Full Text] [PDF]

				F. F. Lang and M. R. Gilbert Diffusely Infiltrative Low-Grade Gliomas in Adults J. Clin. Oncol., March 10, 2006; 24(8): 1236 - 1245. [Abstract] [Full Text] [PDF]

				R. Stupp, M. E. Hegi, M. J. van den Bent, W. P. Mason, M. Weller, R. O. Mirimanoff, J. G. Cairncross, and on behalf of the European Organisation for Researc Changing paradigms--an update on the multidisciplinary management of malignant glioma. Oncologist, February 1, 2006; 11(2): 165 - 180. [Abstract] [Full Text] [PDF]

				K. E. Warren, A. A. Aikin, M. Libucha, B. C. Widemann, E. Fox, R. J. Packer, and F. M. Balis Phase I Study of O6-Benzylguanine and Temozolomide Administered Daily for 5 Days to Pediatric Patients With Solid Tumors J. Clin. Oncol., October 20, 2005; 23(30): 7646 - 7653. [Abstract] [Full Text] [PDF]

				M. S. Bobola, J. R. Silber, R. G. Ellenbogen, J. R. Geyer, A. Blank, and R. D. Goff O6-Methylguanine-DNA Methyltransferase, O6-Benzylguanine, and Resistance to Clinical Alkylators in Pediatric Primary Brain Tumor Cell Lines Clin. Cancer Res., April 1, 2005; 11(7): 2747 - 2755. [Abstract] [Full Text] [PDF]

				E. Greanya, S. Taylor, F H. BscPharm, J Barnett, and B Thiessen Temozolomide for malignant gliomas in British Columbia: A population-based cost-effectiveness analysis Journal of Oncology Pharmacy Practice, December 1, 2004; 10(4): 201 - 209. [Abstract] [PDF]

				M. S. Bobola, M. J. Emond, A. Blank, E. H. Meade, D. D. Kolstoe, M. S. Berger, R. C. Rostomily, D. L. Silbergeld, A. M. Spence, and J. R. Silber Apurinic Endonuclease Activity in Adult Gliomas and Time to Tumor Progression after Alkylating Agent-Based Chemotherapy and after Radiotherapy Clin. Cancer Res., December 1, 2004; 10(23): 7875 - 7883. [Abstract] [Full Text] [PDF]

				K. Hoang-Xuan, L. Capelle, M. Kujas, S. Taillibert, H. Duffau, J. Lejeune, M. Polivka, E. Criniere, Y. Marie, K. Mokhtari, et al. Temozolomide As Initial Treatment for Adults With Low-Grade Oligodendrogliomas or Oligoastrocytomas and Correlation With Chromosome 1p Deletions J. Clin. Oncol., August 1, 2004; 22(15): 3133 - 3138. [Abstract] [Full Text] [PDF]

				M. Sanson, S. Cartalat-Carel, S. Taillibert, M. Napolitano, L. Djafari, J. Cougnard, H. Gervais, F. Laigle, A. Carpentier, K. Mokhtari, et al. Initial chemotherapy in gliomatosis cerebri Neurology, July 27, 2004; 63(2): 270 - 275. [Abstract] [Full Text] [PDF]

				N. Levin, J. M. Gomori, and T. Siegal Chemotherapy as initial treatment in gliomatosis cerebri: Results with temozolomide Neurology, July 27, 2004; 63(2): 354 - 356. [Abstract] [Full Text] [PDF]

				J. J. Raizer, M. G. Malkin, M. Kleber, and L. E. Abrey Phase 1 study of 28-day, low-dose temozolomide and BCNU in the treatment of malignant gliomas after radiation therapy Neuro-oncol, July 1, 2004; 6(3): 247 - 252. [Abstract] [PDF]

				C. Lebrun, D. Fontaine, A. Ramaioli, F. Vandenbos, S. Chanalet, M. Lonjon, J. F. Michiels, V. Bourg, P. Paquis, M. Chatel, et al. Long-term outcome of oligodendrogliomas Neurology, May 25, 2004; 62(10): 1783 - 1787. [Abstract] [Full Text] [PDF]

				M. Brada, L. Viviers, C. Abson, F. Hines, J. Britton, S. Ashley, S. Sardell, D. Traish, A. Gonsalves, P. Wilkins, et al. Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas Ann. Onc., December 1, 2003; 14(12): 1715 - 1721. [Abstract] [Full Text] [PDF]

				A. Pace, A. Vidiri, E. Galie, M. Carosi, S. Telera, A. M. Cianciulli, P. Canalini, D. Giannarelli, B. Jandolo, and C. M. Carapella Temozolomide chemotherapy for progressive low-grade glioma: clinical benefits and radiological response Ann. Onc., December 1, 2003; 14(12): 1722 - 1726. [Abstract] [Full Text] [PDF]

				P. Brown and J. Buckner Temozolomide: Too Early for Definitive Conclusions J. Clin. Oncol., October 1, 2003; 21(19): 3710 - 3710. [Full Text] [PDF]