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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 [6]
- Ewing sarcoma [4]
- islet cell tumor [4]
Dosage:
1) start: 150-200 PO mg/m2/day for 5 days of 30 day cycle
2) postpone next dose until:
a) absolute neutrophil count > 1500/m3
b) platelet count > 100,000/mm3
3) if absolute neutrophil count drops < 1000/mm3, or platelet count drops < 50,000/mm3, reduce next dose by 50 mg/m2/day
4) capsules should be taken on an empty stomach, preferably at bedtime
5) 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 [5]
Pharmacokinetics:
-> good penetration of blood brain barrier [3]
Adverse effects:
1) myelosuppression
a) neutropenia & thrombocytopenia
b) nadir at 22-28 days
2) nausea/vomiting (50%)
3) headache (41%)
4) constipation (33%)
5) convulsions (23%)
6) hemiparesis (18%)
7) diarrhea (16%)
8) fever (13%)
9) asthenia (13%)
10) dizziness (12%)
11) amnesia (10%)
12) insomnia (10%)
Mechanism of action:
1) oral imidazotetrazine derivative
2) parent compound is not cytotoxic
3) rapidly hydrolyzed to active metabolite monomethyl triazenoimidazole carboxamide (MTIC)
4) MTIC is an alkylating agent, alkylating O6 & N7 positions of guanine
Interactions
drug adverse effects of alkylating agents
General
alkylating agent triazene
Database Correlations
PUBCHEM cid=5394
References
- Kaiser Permanente Pharmacy update
- Kaiser Permanente Northern California Regional Drug
Formulary, 2000
- Levin et al, Neoplasms of the central nervous system, in:
Cancer: Principles & Practice of Oncology, DeVita et al,
eds, Lippincott, Williams & Wilkins, Philadelphia, 2001,
pg 2119
- Deprecated Reference
- Medical Knowledge Self Assessment Program (MKSAP) 17,
American College of Physicians, Philadelphia 2015
- Perry JR, Laperriere N, O'Callaghan CJ
Short-Course Radiation plus Temozolomide in Elderly Patients
with Glioblastoma.
N Engl J Med 2017; 376:1027-1037. March 16, 2017
PMID: 28296618
http://www.nejm.org/doi/full/10.1056/NEJMoa1611977