temozolomide (Temodar, Methazolastone)

Indications

• refractory anaplastic astrocytoma (FDA approved use)
• metastatic malignant melanoma
• glioblastoma multiforme at 1st relapse
• used in connection with radiation therapy for glioblastoma
• Ewing sarcoma
• islet cell tumor

Dosage

• start: 150-200 PO mg/m2/day for 5 days of 30 day cycle
• postpone next dose until:
  • absolute neutrophil count > 1500/m3
  • platelet count > 100,000/mm3
• if absolute neutrophil count drops < 1000/mm3, or platelet count drops < 50,000/mm3, reduce next dose by 50 mg/m2/day
• capsules should be taken on an empty stomach, preferably at bedtime
• do NOT open, crush or chew capsules

Capsules: 5 mg, 20 mg, 100 mg, 250 mg.

prophylaxis for pneumocystis pneumonia indicated with prolonged daily therapy

Pharmacokinetics

• good penetration of blood brain barrier

Adverse effects

• myelosuppression
  • neutropenia & thrombocytopenia
  • nadir at 22-28 days
• nausea/vomiting (50%)
• headache (41%)
• constipation (33%)
• convulsions (23%)
• hemiparesis (18%)
• diarrhea (16%)
• fever (13%)
• asthenia (13%)
• dizziness (12%)
• amnesia (10%)
• insomnia (10%)

• drug adverse effects of alkylating agents

Mechanism of action

• oral imidazotetrazine derivative
• parent compound is not cytotoxic
• rapidly hydrolyzed to active metabolite monomethyl triazenoimidazole carboxamide (MTIC)
• MTIC is an alkylating agent, alkylating O6 & N7 positions of guanine

More general terms

• alkylating agent triazene

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5394