Temozolomide

Temozolomide is an oral and intravenous chemotherapy medicine belonging to the alkylating-agent class. It is used to treat certain malignant brain tumours, particularly glioblastoma and anaplastic astrocytoma, according to the approved indication and treatment setting. Temozolomide works by chemically modifying DNA within tumour cells, particularly through methylation of DNA bases. This damage interferes with DNA replication and cell division, which can lead to tumour-cell death. The medicine can cross the blood–brain barrier, an important feature when treating cancers located in the brain. It may be prescribed alongside radiotherapy, followed by maintenance chemotherapy, or as treatment for selected tumours that have returned or progressed after earlier therapy. Treatment schedules vary according to the tumour type, previous treatment, blood counts and the patient's overall health. Although temozolomide can help control tumour growth, its effectiveness varies and it does not guarantee a cure. Because it can suppress bone-marrow function and affect the immune system, treatment requires regular blood tests and clinical assessment. Liver function also needs monitoring. Patients should take the medicine exactly as prescribed and report fever, unusual bruising, bleeding, persistent vomiting or other concerning symptoms to their healthcare team.

Temozolomide was developed as an oral alkylating chemotherapy agent capable of reaching the central nervous system. After administration, it is converted into an active compound that damages tumour-cell DNA and interferes with cell division. The United States Food and Drug Administration (FDA) first approved temozolomide in 1999 for selected malignant brain tumours. The European Commission granted marketing authorisation for Temodal in the European Union on 26 January 1999. A major clinical advance came from the EORTC-NCIC phase 3 trial, published in 2005, which demonstrated improved survival when temozolomide was added to radiotherapy for newly diagnosed glioblastoma. Subsequent studies evaluated its use in recurrent malignant gliomas and anaplastic astrocytoma. On 14 September 2023, the FDA updated temozolomide labelling under its Project Renewal initiative, including indications for adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma and treatment of adults with refractory anaplastic astrocytoma. Approved uses and age criteria differ across jurisdictions, so clinicians should consult the current local prescribing information.

Temozolomide is used to treat selected malignant brain tumours. In adults with newly diagnosed glioblastoma, it is administered alongside radiotherapy and then continued as maintenance chemotherapy. In the United States, approved indications also include adjuvant treatment of adults with newly diagnosed anaplastic astrocytoma and treatment of adults with refractory anaplastic astrocytoma. In the European Union, temozolomide is authorised for newly diagnosed glioblastoma in adults and for certain recurrent or progressive malignant gliomas, including glioblastoma and anaplastic astrocytoma, in adults and children aged three years and older. Monotherapy may be used in selected recurrent or progressive disease, depending on the applicable indication. Treatment choice depends on tumour type, previous therapy, molecular and pathological findings, the patient's general condition and local clinical guidelines. Use for other cancers is investigational unless specifically authorised.

Temozolomide is administered orally as capsules or intravenously as an infusion. The dose is calculated using body surface area and varies according to tumour type, treatment phase, previous therapy and tolerance. For newly diagnosed glioblastoma, a common regimen involves daily treatment during a course of focal radiotherapy, followed by maintenance cycles in which the medicine is taken daily for five consecutive days of each 28-day cycle. Maintenance treatment commonly continues for six cycles, although the treating specialist determines the appropriate duration. For selected anaplastic astrocytoma indications, treatment may involve five-day courses repeated every 28 days, with the total number of cycles depending on the indication and response. Capsules should be swallowed whole with water and should not be opened, chewed or dissolved. Intravenous treatment is administered by trained healthcare professionals. Antiemetic medication and Pneumocystis pneumonia prophylaxis may be required in relevant settings. Blood counts and liver function must be monitored, and doses may need to be delayed, reduced or stopped for toxicity.

Common side effects of temozolomide include nausea, vomiting, constipation, reduced appetite, fatigue, headache and hair loss. Some patients experience rash, seizures related to the underlying brain tumour or treatment, and reduced blood-cell counts. Low platelet counts may increase bruising or bleeding, while low neutrophil counts can raise the risk of infection. Lymphocyte reduction may also weaken immune defences. Side effects vary according to the treatment schedule, dose, previous therapies and individual health. Nausea and vomiting may often be managed with prescribed antiemetics, while fatigue and appetite changes may require supportive care. Patients should report persistent vomiting, fever, unusual bruising, bleeding or worsening symptoms promptly. Regular monitoring helps the clinical team identify adverse effects early and determine whether supportive treatment or a dose adjustment is needed.

Temozolomide can cause significant bone-marrow suppression, including severe neutropenia, thrombocytopenia and lymphopenia. These changes can lead to serious infections or bleeding and may require treatment interruption or discontinuation. Severe and sometimes fatal liver injury has been reported, so liver function must be monitored before and during treatment and after the final dose as directed by the prescribing information. Pneumocystis jirovecii pneumonia is an important risk, particularly during concurrent radiotherapy, when corticosteroids are used or when lymphocyte counts are low. Rare secondary cancers, including myelodysplastic syndrome and myeloid leukaemia, have also been reported. Temozolomide can cause fetal harm and requires appropriate pregnancy-prevention counselling. It is contraindicated in patients with a history of serious hypersensitivity to temozolomide, its ingredients or dacarbazine, and severe myelosuppression is a major treatment concern. Clinicians should assess serious toxicity promptly and adjust or discontinue treatment when indicated.

Before starting temozolomide, clinicians should assess complete blood counts, liver function, kidney function where clinically relevant, infection risks, pregnancy status when applicable and the patient's previous chemotherapy exposure. Blood counts should be checked before treatment cycles and at other specified intervals, while liver tests are required at baseline, during early treatment, before subsequent cycles and after treatment as directed by the product information. Patients receiving concurrent radiotherapy or prolonged corticosteroids may require Pneumocystis pneumonia prophylaxis. Pregnancy should be avoided during treatment, and patients should discuss effective contraception, fertility and breastfeeding with their oncology team. Temozolomide should be reviewed carefully alongside other medicines that suppress bone-marrow function or increase infection risk. Valproic acid can modestly reduce temozolomide clearance, and the overall medication regimen should be reviewed for clinically relevant effects. Patients should not handle damaged capsules or open them themselves; any accidental exposure should be managed according to pharmacy and product-handling guidance.

Confirm the tumour diagnosis, treatment indication, body-surface-area calculation and planned treatment schedule before dispensing or administering temozolomide. Review baseline blood counts and liver function, and arrange repeat testing in accordance with the selected regimen. Provide clear written instructions distinguishing the radiotherapy-concurrent phase from maintenance cycles, particularly the five-day dosing period and the planned break between cycles. Check that antiemetic medication and Pneumocystis pneumonia prophylaxis are prescribed when indicated. Counsel patients to swallow capsules whole, avoid handling damaged capsules and contact the oncology team promptly if a dose is missed or vomiting occurs after a dose rather than taking an extra dose independently. Monitor for fever, bleeding, persistent gastrointestinal symptoms, jaundice or unusual fatigue. Pharmacists should verify capsule strengths and total daily doses carefully, since dosing errors can cause serious toxicity. Coordinate care with oncology, radiation oncology, nursing and pharmacy teams, and reassess treatment continuation according to tumour response, tolerability and laboratory findings.