Written By: Hassaan Shaikh, PharmD & Emily Brugioni, MD, University Health

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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

PQI Process:

  • 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

ToxicityTherapy InterruptionTherapy Discontinuation
Absolute Neutrophil CountGreater than or equal to 0.5 and less than 1.5 x 109/LLess than 0.5 x 109/L
Platelet CountGreater than or equal to 10 and less than 100 x 109/LLess than 10 x 109/L
Common Toxicity Criteria (CTC) non-hematological Toxicity (except for alopecia, nausea, vomiting)CTC Grade 2CTC Grade 3 or 4

 

Temozolomide Dose Levels for Maintenance Treatment2

Dose levelDose (mg/m2/day)Remarks
-1100Reduction for prior toxicity
0150Dose during Cycle 1
1200Dose during Cycles 2-6 in absence of toxicity

 

Temozolomide Dose Reduction or Discontinuation during Maintenance Treatment2

ToxicityReduce Temozolomide by 1 Dose LevelDiscontinue Temozolomide
Absolute Neutrophil CountLess than 1.0 x 109/LDiscontinue 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 CountLess than 50 x 109 /L
Common Toxicity Criteria (CTC) Non Hematological Toxicity

(except for alopecia, nausea, vomiting)

CTC Grade 3CTC 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

References:

  1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Central Nervous System Cancers. V.2.2021, 09/08/21.
  2. Temozolomide [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.
  3. 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.
  4. 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.
Important notice: NCODA has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.

 

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