TEMACCORD

What it is

TEMACCORD contains temozolomide as the active ingredient, available in strengths of 5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg. Temozolomide is an imidazotetrazine alkylating agent with anti-tumour activity that undergoes rapid chemical conversion in the systemic circulation at physiological pH to the active compound, monomethyl triazeno imidazole carboxamide (MTIC).

Approved indications

— Newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as adjuvant treatment — Recurrence of anaplastic astrocytoma and glioblastoma multiforme following standard therapy — Advanced metastatic malignant melanoma as first-line treatment

Dosing overview

For newly diagnosed glioblastoma multiforme during the concomitant phase, TEMACCORD is administered orally at 75 mg/m² daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions) followed by adjuvant temozolomide for six cycles. Dosage in adjuvant cycle 1 is 150 mg/m² once daily for five days followed by 23 days without treatment. At the start of cycle 2, the dose is escalated to 200 mg/m² if toxicity criteria are met. For recurrent glioblastoma multiforme or anaplastic astrocytoma in patients previously untreated with chemotherapy, temozolomide is administered orally at 200 mg/m² once daily for five days per 28 day cycle, or 150 mg/m² for those previously treated with chemotherapy, to be increased in the second cycle to 200 mg/m² if blood count criteria are met. For metastatic malignant melanoma, the recommended dose is 200 mg/m² once daily for five days per 28 day cycle.

Key safety warnings

Patients who received concomitant TEMACCORD and radiotherapy for the prolonged 42 day schedule are at particular risk for developing Pneumocystis carinii pneumonia (PCP), and prophylaxis against PCP is required for all patients receiving concomitant temozolomide and radiotherapy for the 42 day regimen regardless of lymphocyte count. Hepatic injury, including fatal hepatic failure, has been reported very rarely in patients treated with temozolomide. Baseline liver function tests should be performed prior to treatment initiation, and if abnormal, physicians should assess the benefit/risk prior to initiating TEMACCORD including the potential for fatal hepatic failure. Hepatitis due to hepatitis B virus (HBV) reactivation, in some cases resulting in death, has been reported. Patients should be screened for HBV infection before treatment initiation, monitored during and for several months following treatment, and therapy should be discontinued for patients with evidence of active hepatitis B infection. TEMACCORD causes myelosuppression and patients may experience prolonged pancytopenia, which may result in aplastic anaemia, which in some cases has resulted in a fatal outcome. Prior to dosing, absolute neutrophil count (ANC) must be greater than 1.5 x 10⁹/L and platelets greater than 100 x 10⁹/L. During cyclical treatment a complete blood count must be obtained on day 22 or within 48 hours of that day, and weekly until ANC is above 1.5 x 10⁹/L and platelet count exceeds 100 x 10⁹/L.

Contraindications

TEMACCORD is contraindicated in patients who have a history of hypersensitivity reaction to components of temozolomide or to dacarbazine (DTIC). Use is contraindicated during pregnancy and in women who intend to become pregnant. TEMACCORD is contraindicated in patients with severe myelosuppression. TEMACCORD must not be used by breastfeeding women.

Regulatory history

TEMACCORD was first registered on the Australian Register of Therapeutic Goods on 19 July 2011 with six capsule formulations in bottles (5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg strengths). On 13 June 2013, an additional six sachet formulations of the same strengths were registered.