II. Indications

  1. FDA Approved
    1. Anaplastic Astrocytoma
    2. Glioblastoma Multiforme
  2. Off Label (typically recurrent or refractory neoplasms)
    1. Cutaneous T Cell Lymphoma
    2. Ewing Sarcoma
    3. Lymphoma (CNS)
    4. Metastatic Melanoma
    5. Neuroblastoma (children)
    6. Neuroendocrine Tumors (e.g. Carcinoid Tumor)
    7. Renal Cell Carcinoma
    8. Soft Tissue Sarcoma

III. Mechanism

  1. See Alkylating Agent
  2. Triazene Alkylating Agent, an analog of Dacarbazine
  3. Temozolomide is a prodrug activated at physiologic pH to MTIC (monomethyl triazeno imidazole carboxamide)
    1. Contrast with Dacarbazine which is only metabolized to active MTIC in the liver
  4. MTIC methylates DNA at guanine's O6 and N7
    1. Inhibits DNA Replication
    2. Similar activity to Dacarbazine

IV. Medications

  1. Capsule: Various from 5 mg to 250 mg
  2. Lyophilized injection powder for IV Solution: 100 mg

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Pharmacokinetics

  1. Good CNS penetration

VII. Adverse Effects

  1. Alopecia
  2. Bone Marrow Suppression
  3. Secondary Malignancy
  4. Impaired future fertility
  5. Respiratory (interstitial pneumonitis, pulmonary fibrosis)
  6. Opportunistic infections (CMV, Hepatitis B)

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in Pregnancy (all trimesters)
    1. Use reliable Contraception
  3. Monitoring
    1. Complete Blood Count

IX. Drug Interactions

  1. Valproic Acid
    1. Raises Temozolomide levels by decreasing clearance

XI. References

Images: Related links to external sites (from Bing)

Related Studies

Ontology: temozolomide (C0076080)

Definition (NCI_NCI-GLOSS) A drug that is used to treat certain types of brain tumors in adults and is being studied in the treatment of other types of cancer. It belongs to the family of drugs called alkylating agents.
Definition (NCI) A triazene analog of dacarbazine with antineoplastic activity. As a cytotoxic alkylating agent, temozolomide is converted at physiologic pH to the short-lived active compound, monomethyl triazeno imidazole carboxamide (MTIC). The cytotoxicity of MTIC is due primarily to methylation of DNA at the O6 and N7 positions of guanine, resulting in inhibition of DNA replication. Unlike dacarbazine, which is metabolized to MITC only in the liver, temozolomide is metabolized to MITC at all sites. Temozolomide is administered orally and penetrates well into the central nervous system. (NCI04)
Definition (CSP) dacarbazine derivative; alkylating antineoplastic agent.
Definition (PDQ) A triazene analog of dacarbazine with antineoplastic activity. As a cytotoxic alkylating agent, temozolomide is converted at physiologic pH to the short-lived active compound, monomethyl triazeno imidazole carboxamide (MTIC). The cytotoxicity of MTIC is due primarily to methylation of DNA at the O6 and N7 positions of guanine, resulting in inhibition of DNA replication. Unlike dacarbazine, which is metabolized to MITC only in the liver, temozolomide is metabolized to MITC at all sites. Temozolomide is administered orally and penetrates well into the central nervous system. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41671&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41671&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1244" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C047246
SnomedCT 327037001, 116099008, 387009002
English 8-carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one, methazolastone, 3,4-dihydro-3-methyl-4-oxoimidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one, imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, temozolomide, temozolomide (medication), temozolomide [Chemical/Ingredient], TEMOZOLOMIDE, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, Methazolastone, Temozolomide (product), Temozolomide (substance), Temozolomide, TMZ
Spanish temozolomida (producto), temozolomida (sustancia), temozolomida