| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Minireview |
Departments of Surgery, Medicine, and Pediatrics [H. S. F.] and Department of Pathology [T. K.], Duke University, Durham, North Carolina 27710, and Division of Oncology, Newcastle General Hospital, Newcastle Upon Tyne, NE4 6BE United Kingdom [H. C.]
Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more frequently than other types of primary central nervous system tumors, having a combined incidence of 5–8/100,000 population. Even with aggressive treatment using surgery, radiation, and chemotherapy, median reported survival is less than 1 year. Temozolomide, a new drug, has shown promise in treating malignant gliomas and other difficult-to-treat tumors.
Temozolomide, a p.o. imidazotetrazine second-generation alkylating agent, is the leading compound in a new class of chemotherapeutic agents that enter the cerebrospinal fluid and do not require hepatic metabolism for activation. In vitro, temozolomide has demonstrated schedule-dependent antitumor activity against highly resistant malignancies, including high-grade glioma. In clinical studies, temozolomide consistently demonstrates reproducible linear pharmacokinetics with approximately 100% p.o. bioavailability, noncumulative minimal myelosuppression that is rapidly reversible, and activity against a variety of solid tumors in both children and adults. Preclinical studies have evaluated the combination of temozolomide with other alkylating agents and inhibitors of the DNA repair protein O6-alkylguanine alkyltransferase to overcome resistance to chemotherapy in malignant glioma and malignant metastatic melanoma. Temozolomide has recently been approved in the United States for the treatment of adult patients with refractory anaplastic astrocytoma and, in the European Union, for treatment of glioblastoma multiforme showing progression or recurrence after standard therapy. Predictable bioavailability and minimal toxicity make temozolomide a candidate for a wide range of clinical testing to evaluate the potential of combination treatments in different tumor types. An overview of the mechanism of action of temozolomide and a summary of results from clinical trials in malignant glioma are presented here.
This article has been cited by other articles:
|
|
 |
|
  J. J. Virrey, S. Guan, W. Li, A. H. Schonthal, T. C. Chen, and F. M. Hofman Increased Survivin Expression Confers Chemoresistance to Tumor-Associated Endothelial Cells Am. J. Pathol., August 1, 2008; 173(2): 575 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Kil, D. Cerna, W. E. Burgan, K. Beam, D. Carter, P. S. Steeg, P. J. Tofilon, and K. Camphausen In vitro and In vivo Radiosensitization Induced by the DNA Methylating Agent Temozolomide Clin. Cancer Res., February 1, 2008; 14(3): 931 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Alonso, C. Gomez-Manzano, B. N. Bekele, W.K. A. Yung, and J. Fueyo Adenovirus-Based Strategies Overcome Temozolomide Resistance by Silencing the O6-Methylguanine-DNA Methyltransferase Promoter Cancer Res., December 15, 2007; 67(24): 11499 - 11504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Horton, P. A. Thompson, S. L. Berg, P. C. Adamson, A. M. Ingle, M. E. Dolan, S. M. Delaney, M. Hedge, H. L. Weiss, M.-F. Wu, et al. Phase I Pharmacokinetic and Pharmacodynamic Study of Temozolomide in Pediatric Patients With Refractory or Recurrent Leukemia: A Children's Oncology Group Study J. Clin. Oncol., November 1, 2007; 25(31): 4922 - 4928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stupp, M. E. Hegi, M. R. Gilbert, and A. Chakravarti Chemoradiotherapy in Malignant Glioma: Standard of Care and Future Directions J. Clin. Oncol., September 10, 2007; 25(26): 4127 - 4136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hansen, R. Nagasubramanian, S. M. Delaney, L. D. Samson, and M.E. Dolan Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice Carcinogenesis, May 1, 2007; 28(5): 1111 - 1116. [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]
|
|
|
|
|
|
A. Chakravarti, M. G. Erkkinen, U. Nestler, R. Stupp, M. Mehta, K. Aldape, M. R. Gilbert, P. McL. Black, and J. S. Loeffler Temozolomide-Mediated Radiation Enhancement in Glioblastoma: A Report on Underlying Mechanisms Clin. Cancer Res., August 1, 2006; 12(15): 4738 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Jones-Bolin, H. Zhao, K. Hunter, A. Klein-Szanto, and B. Ruggeri The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. Mol. Cancer Ther., July 1, 2006; 5(7): 1744 - 1753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Reardon, J. N. Rich, H. S. Friedman, and D. D. Bigner Recent Advances in the Treatment of Malignant Astrocytoma J. Clin. Oncol., March 10, 2006; 24(8): 1253 - 1265. [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]
|
|
|
|
|
|
M. H. Cohen, J. R. Johnson, and R. Pazdur Food and Drug Administration Drug Approval Summary: Temozolomide Plus Radiation Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme Clin. Cancer Res., October 1, 2005; 11(19): 6767 - 6771. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
B. Yamini, X. Yu, G. Y. Gillespie, D. W. Kufe, and R. R. Weichselbaum Transcriptional Targeting of Adenovirally Delivered Tumor Necrosis Factor {alpha} by Temozolomide in Experimental Glioblastoma Cancer Res., September 15, 2004; 64(18): 6381 - 6384. [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]
|
|
|
|
|
|
D. A. Reardon, J. A. Quinn, J. N. Rich, S. Gururangan, J. Vredenburgh, J. H. Sampson, J. M. Provenzale, A. Walker, M. Badruddoja, S. Tourt-Uhlig, et al. Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma Neuro-oncol, April 1, 2004; 6(2): 134 - 144. [Abstract] [PDF]
|
|
|
|
|
|
N. J. Curtin, L.-Z. Wang, A. Yiakouvaki, S. Kyle, C. A. Arris, S. Canan-Koch, S. E. Webber, B. W. Durkacz, H. A. Calvert, Z. Hostomsky, et al. Novel Poly(ADP-ribose) Polymerase-1 Inhibitor, AG14361, Restores Sensitivity to Temozolomide in Mismatch Repair-Deficient Cells Clin. Cancer Res., February 1, 2004; 10(3): 881 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Chua, M. A. Rosenthal, S. S. Wong, D. M. Ashley, A.-m. Woods, A. Dowling, and L. M. Cher Phase 2 study of temozolomide and Caelyx in patients with recurrent glioblastoma multiforme Neuro-oncol, January 1, 2004; 6(1): 38 - 43. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Vera, L. Djafari, S. Faivre, J.-S. Guillamo, K. Djazouli, M. Osorio, F. Parker, C. Cioloca, B. Abdulkarim, J.-P. Armand, et al. Dose-dense regimen of temozolomide given every other week in patients with primary central nervous system tumors Ann. Onc., January 1, 2004; 15(1): 161 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. G. Johns, R. B. Luwor, C. Murone, F. Walker, J. Weinstock, A. A. Vitali, R. M. Perera, A. A. Jungbluth, E. Stockert, L. J. Old, et al. Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478 PNAS, December 23, 2003; 100(26): 15871 - 15876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tentori, C. Leonetti, M. Scarsella, G. d'Amati, M. Vergati, I. Portarena, W. Xu, V. Kalish, G. Zupi, J. Zhang, et al. Systemic Administration of GPI 15427, a Novel Poly(ADP-Ribose) Polymerase-1 Inhibitor, Increases the Antitumor Activity of Temozolomide against Intracranial Melanoma, Glioma, Lymphoma Clin. Cancer Res., November 1, 2003; 9(14): 5370 - 5379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Persons, E. R. Allay, N. Sawai, P. W. Hargrove, T. P. Brent, H. Hanawa, A. W. Nienhuis, and B. P. Sorrentino Successful treatment of murine {beta}-thalassemia using in vivo selection of genetically modified, drug-resistant hematopoietic stem cells Blood, July 15, 2003; 102(2): 506 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Gilbert, H. S. Friedman, J. F. Kuttesch, M. D. Prados, J. J. Olson, G. H. Reaman, and S. L. Zaknoen A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy Neuro-oncol, October 1, 2002; 4(4): 261 - 267. [Abstract] [PDF]
|
|
|
|
|
|
M. B. Atkins, J. A. Gollob, J. A. Sosman, D. F. McDermott, L. Tutin, P. Sorokin, R. A. Parker, and J. W. Mier A Phase II Pilot Trial of Concurrent Biochemotherapy with Cisplatin, Vinblastine, Temozolomide, Interleukin 2, and IFN-{alpha}2B in Patients with Metastatic Melanoma Clin. Cancer Res., October 1, 2002; 8(10): 3075 - 3081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Bocangel, S. Finkelstein, S. C. Schold, K. K. Bhakat, S. Mitra, and D. M. Kokkinakis Multifaceted Resistance of Gliomas to Temozolomide Clin. Cancer Res., August 1, 2002; 8(8): 2725 - 2734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stupp, P.-Y. Dietrich, S. O. Kraljevic, A. Pica, I. Maillard, P. Maeder, R. Meuli, R. Janzer, G. Pizzolato, R. Miralbell, et al. Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide J. Clin. Oncol., March 1, 2002; 20(5): 1375 - 1382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benjelloun, J. Delavelle, F. Lazeyras, and P.-Y. Dietrich Possible efficacy of temozolomide in a patient with gliomatosis cerebri Neurology, November 27, 2001; 57(10): 1932 - 1932. [Full Text] [PDF]
|
|
|
|
|
|
J. Ma, S. Pulfer, S. Li, J. Chu, K. Reed, and J. M. Gallo Pharmacodynamic-mediated Reduction of Temozolomide Tumor Concentrations by the Angiogenesis Inhibitor TNP-470 Cancer Res., July 1, 2001; 61(14): 5491 - 5498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kokkinakis, R. M. Hoffman, E. P. Frenkel, J. B. Wick, Q. Han, M. Xu, Y. Tan, and S. C. Schold Synergy between Methionine Stress and Chemotherapy in the Treatment of Brain Tumor Xenografts in Athymic Mice Cancer Res., May 1, 2001; 61(10): 4017 - 4023. [Abstract] [Full Text]
|
|
|
|
|
|
V. J. Patel, G. B. Elion, P. J. Houghton, S. Keir, A. E. Pegg, S. P. Johnson, M. E. Dolan, D. D. Bigner, and H. S. Friedman Schedule-dependent Activity of Temozolomide plus CPT-11 against a Human Central Nervous System Tumor-derived Xenograft Clin. Cancer Res., October 1, 2000; 6(10): 4154 - 4157. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
