Written By: Hassaan Shaikh, PharmD & Emily Brugioni, MD, University Health
Description: The purpose of this PQI is a summary of the process for initiating and monitoring oral temozolomide therapy in patients with Glioblastoma Multiforme (GBM).
Background: GBM is the most common primary malignant brain tumor in adults and comprises 54 % of all gliomas with a median survival of 6 to 12 months.1 Temozolomide is an FDA approved medication used to treat GBM.2 Temozolomide is a prodrug that is converted into its active alkylating metabolite which causes DNA double strand breaks and apoptosis.2 Concurrent treatment with temozolomide and radiation followed by a 4 week break, then maintenance temozolomide for 5 days every 28 days for 6 cycles was found to improve 2 year survival from 10.4% (radiation alone) to 26.5% (radiation + temozolomide).3 Furthermore, patients with MGMT promoter methylated GBM were shown to have a better 18-month overall survival with concurrent temozolomide and radiation (62%) when compared with unmethylated MGMT (8%).4
- Ensure appropriate indication and dose, keeping in mind that dose modifications occurred frequently in the clinical trials
- Temozolomide 75 mg/m2 PO daily during radiation followed by a 4 week break, then 150-200 mg/m2 PO daily x 5 every 28 days for 6 cycles2
- Concurrent temozolomide with radiation can cause lymphocytopenia therefore ensure appropriate prophylaxis of Pneumocystis Jiroveci with oral trimethoprim-sulfamethoxazole, inhaled pentamidine, atovaquone or dapsone2
- Ondansetron should be prescribed for prevention and treatment of nausea and vomiting; if nausea and vomiting occurs, ondansetron may be taken 30-60 minutes prior to temozolomide2
- Monitor pregnancy, CBC (lymphopenia, thrombocytopenia), liver enzymes, pneumocystis2
Dosing Interruption or Discontinuation during Concomitant Radiotherapy and Temozolomide2
|Toxicity||Therapy Interruption||Therapy Discontinuation|
|Absolute Neutrophil Count||Greater than or equal to 0.5 and less than 1.5 x 109/L||Less than 0.5 x 109/L|
|Platelet Count||Greater than or equal to 10 and less than 100 x 109/L||Less than 10 x 109/L|
|Common Toxicity Criteria (CTC) non-hematological Toxicity (except for alopecia, nausea, vomiting)||CTC Grade 2||CTC Grade 3 or 4|
Temozolomide Dose Levels for Maintenance Treatment2
|Dose level||Dose (mg/m2/day)||Remarks|
|-1||100||Reduction for prior toxicity|
|0||150||Dose during Cycle 1|
|1||200||Dose during Cycles 2-6 in absence of toxicity|
Temozolomide Dose Reduction or Discontinuation during Maintenance Treatment2
|Toxicity||Reduce Temozolomide by 1 Dose Level||Discontinue Temozolomide|
|Absolute Neutrophil Count||Less than 1.0 x 109/L||Discontinue if dose reduction to less than 100 mg/m2 is required or if the same Grade 3 non hematological toxicity (except for alopecia, nausea, vomiting) recurs after dose reduction|
|Platelet Count||Less than 50 x 109 /L|
|Common Toxicity Criteria (CTC) Non Hematological Toxicity|
(except for alopecia, nausea, vomiting)
|CTC Grade 3||CTC Grade 4|
Temozolomide Dose Modification Table2
Patient Centered Activities:
- Provide Oral Chemotherapy Education (OCE) sheet
- Provide Treatment Support Kit (TSK)
- Counsel patient on disease state, treatment regimen, what to expect and verify patient understanding
- Counsel patient on common side effects which include alopecia, constipation, nausea/vomiting, headache, seizure, and fatigue
- Temozolomide is preferred to be taken one hour prior to radiation on radiation days
- Counsel patient to swallow capsules (may be multiple) whole with a full glass of water
- May administer on an empty stomach and/or bedtime to reduce nausea/vomiting and consistently take in this manner
- Do not repeat dose if vomiting occurs after the dose is administered
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. V.2.2021, 09/08/21.
- Temozolomide [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.
- Stupp R, Mason WP, van den Bent MJ, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987-96, 2005.
- Hegi ME, Diserens AC, Godard S, et al: Clinical trial substantiates the predictive value of O-6- methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 10:1871-4, 2004.
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