temozolomide (Temodar, Methazolastone)
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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
- 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[5]
Pharmacokinetics
- good penetration of blood brain barrier[3]
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%)
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
References
- ↑ Kaiser Permanente Pharmacy update
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 2000
- ↑ Jump up to: 3.0 3.1 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
- ↑ Jump up to: 4.0 4.1 4.2 Deprecated Reference
- ↑ Jump up to: 5.0 5.1 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ Jump up to: 6.0 6.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28296618 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1611977