Temozolomide (Specialist drug)

Escalation to 200 mg/m2 at Cycle 2 requires CTC non-haematological toxicity for Cycle 1 Grade 2 or less (except alopecia, nausea, vomiting), ANC 1.5 x 10^9/l or more, and thrombocytes 100 x 10^9/l or more; if not escalated at Cycle 2, do not escalate in later cycles. Concomitant phase: no dose reductions are recommended, but delay or discontinuation is decided weekly on toxicity; treatment may continue through the 42-day period (up to 49 days) only if ANC 1.5 x 10^9/l or more, thrombocytes 100 x 10^9/l or more, and CTC non-haematological toxicity Grade 1 or less (except alopecia, nausea, vomiting). Interrupt if ANC 0.5 to under 1.5 x 10^9/l, thrombocytes 10 to under 100 x 10^9/l, or CTC Grade 2 non-haematological toxicity; discontinue if ANC under 0.5 x 10^9/l, thrombocytes under 10 x 10^9/l, or CTC Grade 3-4 non-haematological toxicity (Table 1). Monotherapy: reduce by one dose level for ANC under 1.0 x 10^9/l, thrombocytes under 50 x 10^9/l, or CTC Grade 3 non-haematological toxicity; discontinue for CTC Grade 4, if 100 mg/m2 still causes unacceptable toxicity, or if the same Grade 3 non-haematological toxicity recurs after reduction (Table 3). Full blood count weekly during the concomitant phase and on Day 22 of each monotherapy cycle. Pneumocystis jirovecii pneumonia prophylaxis is required for all patients on the 42-day concomitant regimen regardless of lymphocyte count. Anti-emetic therapy may be given. OTHER INDICATION — Adult and paediatric patients 3 years of age or older with recurrent or progressive malignant glioma (28-day cycle): chemotherapy-naive patients 200 mg/m2 orally once daily for the first 5 days followed by a 23-day interruption; patients previously treated with chemotherapy start at 150 mg/m2 once daily, increased in the second cycle to 200 mg/m2 once daily for 5 days if there is no haematological toxicity. Paediatric: in patients 3 years of age or older temozolomide is only to be used in recurrent or progressive malignant glioma and experience in these children is very limited; safety and efficacy under 3 years of age have not been established (no data). Elderly (over 70 years) appear to be at increased risk of neutropenia and thrombocytopenia. Hepatic impairment: pharmacokinetics comparable in mild/moderate impairment; no data in severe (Child's Class C) — dose reduction unlikely to be required but caution advised. Only to be prescribed by physicians experienced in the oncological treatment of brain tumours.