Overview
Refractory anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV) are primary malignant brain tumours with poor prognosis and limited treatment options. Despite considerable genetic heterogeneity, these tumours often have impaired DNA repair systems, rendering them initially sensitive to alkylating agents, although they invariably develop resistance to these agents over time. Temozolomide is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; these properties allow for both oral and intravenous administration. Following initial hydrolysis, further reactions liberate a highly reactive methyl diazonium cation capable of methylating various residues on adenosine and guanine bases leading to DNA lesions and eventual apoptosis. Temozomolide as an adjunct to radiotherapy followed by maintenance dosing remains the standard of care for both Glioblastoma and refractory anaplastic astrocytoma. Temozolomide was granted FDA approval on August 11, 1999, as an oral capsule and subsequently on February 27, 2009, as an intravenous injection. It is currently marketed under the trademark TEMODAR® by Merck.
Indication
Temozolomide is indicated in adult patients for the treatment of newly diagnosed glioblastoma concomitantly with radiotherapy and for use as maintenance treatment thereafter. It is also indicated for the treatment of refractory anaplastic astrocytoma in adult patients or adjuvant therapy for adults with newly diagnosed anaplastic astrocytoma.
Associated Conditions
- Advanced Melanoma
- High Grade Glioma: Glioblastoma (GBM)
- Primary Central Nervous System Lymphoma
- Refractory Ewing Sarcoma
- Refractory Neuroblastoma
- Soft Tissue Sarcoma
- Advanced Neuroendocrine tumor
- Newly diagnosed Anaplastic Astrocytoma (AA)
- Refractory Anaplastic astrocytoma
- Refractory, advanced Mycosis fungoides
- Refractory, advanced Sezary Syndrome
Research Report
A Comprehensive Monograph on Temozolomide: Pharmacology, Clinical Efficacy, and Mechanisms of Resistance
Executive Summary
Temozolomide is an oral and intravenous alkylating agent that has fundamentally altered the therapeutic landscape for patients with high-grade malignant gliomas. As an imidazotetrazine derivative, it functions as a prodrug, undergoing non-enzymatic conversion at physiological pH to a reactive species that methylates tumor cell DNA, inducing cytotoxic lesions that lead to apoptosis. Its excellent oral bioavailability and ability to penetrate the blood-brain barrier make it uniquely suited for treating central nervous system malignancies.
The clinical utility of Temozolomide was definitively established by the landmark 2005 phase III trial by Stupp et al., which demonstrated that adding concomitant and adjuvant Temozolomide to standard radiotherapy significantly improved median and long-term survival for patients with newly diagnosed glioblastoma (GBM). This regimen, now known as the "Stupp protocol," was rapidly adopted as the global standard of care. The drug has also proven its efficacy in anaplastic astrocytoma (AA), first in the refractory/recurrent setting and more recently as an adjuvant therapy for newly diagnosed, IDH-mutant tumors.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/07/25 | Not Applicable | Not yet recruiting | |||
2025/06/18 | Phase 1 | Recruiting | Steven DuBois, MD | ||
2025/06/17 | Early Phase 1 | Not yet recruiting | |||
2025/06/11 | Phase 2 | Not yet recruiting | Juno Therapeutics, Inc., a Bristol-Myers Squibb Company | ||
2025/05/31 | Phase 2 | ENROLLING_BY_INVITATION | Yingjuan Zheng | ||
2025/05/30 | Phase 1 | Not yet recruiting | |||
2025/05/25 | Phase 2 | Not yet recruiting | Baptist Health South Florida | ||
2025/04/24 | Early Phase 1 | Not yet recruiting | C17 Council | ||
2025/04/18 | Phase 1 | Recruiting | |||
2025/04/17 | Phase 1 | Not yet recruiting | Nerviano Medical Sciences |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Lannett Company, Inc. | 0527-1778 | ORAL | 20 mg in 1 1 | 12/1/2015 | |
| Zydus Lifesciences Limited | 70771-1096 | ORAL | 180 mg in 1 1 | 10/17/2022 | |
| Merck Sharp & Dohme LLC | 0085-1430 | ORAL | 180 mg in 1 1 | 9/14/2023 | |
| Zydus Lifesciences Limited | 70771-1097 | ORAL | 250 mg in 1 1 | 10/17/2022 | |
| Ascend Laboratories, LLC | 67877-537 | ORAL | 5 mg in 1 1 | 2/15/2023 | |
| Sun Pharmaceutical Industries, Inc. | 47335-891 | ORAL | 20 mg in 1 1 | 9/13/2023 | |
| Zydus Lifesciences Limited | 70771-1094 | ORAL | 100 mg in 1 1 | 10/17/2022 | |
| Ascend Laboratories, LLC | 67877-542 | ORAL | 250 mg in 1 1 | 2/15/2023 | |
| Areva Pharmaceuticals | 59923-704 | ORAL | 5 mg in 1 1 | 2/2/2024 | |
| Merck Sharp & Dohme LLC | 0085-1366 | ORAL | 100 mg in 1 1 | 9/14/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 1/28/2010 | ||
Authorised | 3/15/2010 | ||
Authorised | 1/25/2010 | ||
Authorised | 1/26/1999 | ||
Authorised | 7/13/2011 | ||
Authorised | 7/13/2011 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| ASTRODAL CAPSULES 20MG | SIN15067P | CAPSULE | 20.0mg | 8/16/2016 | |
| GLIOTEM 20 CAPSULE 20 MG | SIN15641P | CAPSULE | 20.000 mg | 3/1/2019 | |
| GLIOTEM 100 CAPSULE 100 MG | SIN15642P | CAPSULE | 100.000 mg | 3/1/2019 | |
| TemoRel HARD CAPSULE 20MG | SIN15710P | CAPSULE | 20 mg | 6/10/2019 | |
| TemoRel HARD CAPSULE 100MG | SIN15709P | CAPSULE | 100mg | 6/10/2019 | |
| TEMODAL CAPSULE 100 mg | SIN11707P | CAPSULE | 100 mg | 11/1/2001 | |
| ASTRODAL CAPSULES 100MG | SIN15066P | CAPSULE | 100mg | 8/16/2016 | |
| TEMODAL CAPSULE 20 mg | SIN11706P | CAPSULE | 20 mg | 11/1/2001 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| TEMODAL CAP 20MG | N/A | N/A | N/A | 12/10/2005 | |
| JECETEMOZ CAPSULES 100MG | N/A | N/A | N/A | 2/28/2025 | |
| JECETEMOZ CAPSULES 20MG | N/A | N/A | N/A | 2/28/2025 |
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| TEMOZOLOMIDE LUPIN temozolomide 250 mg capsule bottle | 192681 | Medicine | A | 1/7/2013 | |
| TEMACCORD | 172976 | Medicine | A | 7/19/2011 | |
| APO-TEMOZOLOMIDE temozolomide 20mg capsule bottle | 231524 | Medicine | A | 2/19/2015 | |
| TEMACCORD | 206034 | Medicine | A | 6/13/2013 | |
| TEMACCORD | 172977 | Medicine | A | 7/19/2011 | |
| Temozolomide Capsules 180 mg | 280380 | Medicine | A | 9/16/2016 | |
| TEMOZOLOMIDE JUNO temozolomide 100 mg capsule bottle | 354887 | Medicine | A | 4/28/2021 | |
| Temozolomide Capsules 250 mg | 280384 | Medicine | A | 9/16/2016 | |
| APOTEX-Temozolomide temozolomide 250 mg capsule bottle | 206881 | Medicine | A | 2/21/2014 | |
| APO-TEMOZOLOMIDE temozolomide 5 mg capsule bottle | 231523 | Medicine | A | 2/19/2015 |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| JAMP TEMOZOLOMIDE | 02516810 | Capsule - Oral | 100 MG | 7/25/2022 | |
| TEMOZOLOMIDE CAPSULES | mda inc. | 02455749 | Capsule - Oral | 5 MG | N/A |
| TARO-TEMOZOLOMIDE | 02443511 | Capsule - Oral | 100 MG | 7/23/2015 | |
| ACH-TEMOZOLOMIDE | 02389851 | Capsule - Oral | 250 MG | 7/25/2012 | |
| TEVA-TEMOZOLOMIDE | teva canada limited | 02395274 | Capsule - Oral | 20 MG | 11/7/2012 |
| TEMODAL | Merck Canada Inc | 02241096 | Capsule - Oral | 250 MG | 11/12/1999 |
| TEMODAL | Merck Canada Inc | 02241093 | Capsule - Oral | 5 MG | 11/12/1999 |
| ACH-TEMOZOLOMIDE | 02389835 | Capsule - Oral | 140 MG | 7/25/2012 | |
| ACH-TEMOZOLOMIDE | 02389843 | Capsule - Oral | 180 MG | 7/25/2012 | |
| TEMODAL | Merck Canada Inc | 02241094 | Capsule - Oral | 20 MG | 11/12/1999 |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| TEMOZOLOMIDA ACCORD 140 mg CAPSULAS DURAS EFG | 10615014 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOMEDAC 140 mg CAPSULAS DURAS EFG | 09605007 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA SUN 250 mg CAPSULAS DURAS EFG | 11697012 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA SUN 5 mg CAPSULAS DURAS EFG | 11697002 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA ACCORD 140 mg CAPSULAS DURAS EFG | 10615013 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA ACCORD 100 mg CAPSULAS DURAS EFG | 10615010 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOMEDAC 20 mg CAPSULAS DURAS EFG | 09605004 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA SUN 180 mg CAPSULAS DURAS EFG | 11697009 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMODAL 20 MG CAPSULAS DURAS | 98096014 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized | |
| TEMOZOLOMIDA TEVA 20 mg CAPSULAS DURAS EFG | 09606004 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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