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

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