Active Ingredient: Temozolomide
Temozolomide is indicated for the treatment of adult patients with newly-diagnosed glioblastoma multiforme concomitantly with radiotherapy (RT) and subsequently as monotherapy treatment.
For this indication, competent medicine agencies globally authorize below treatments:
Intravenous
75 - 200 mg per m² of body surface area (BSA)
From 75 To 200 mg per m² of body surface area (BSA) once every day
Temozolomide is administered in combination with focal radiotherapy (concomitant phase) followed by up to 6 cycles of temozolomide (TMZ) monotherapy (monotherapy phase).
Temozolomide is administered orally at a dose of 75 mg/m² daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions). No dose reductions are recommended, but delay or discontinuation of temozolomide administration should be decided weekly according to haematological and non-haematological toxicity criteria. Temozolomide administration can be continued throughout the 42 day concomitant period (up to 49 days) if all of the following conditions are met:
During treatment a complete blood count should be obtained weekly. Temozolomide administration should be temporarily interrupted or permanently discontinued during the concomitant phase according to the haematological and non-haematological toxicity criteria as noted in Table 1.
Table 1. Temozolomide dosing interruption or discontinuation during concomitant radiotherapy and temozolomide:
| Toxicity | Temozolomide interruptiona | Temozolomide discontinuation |
|---|---|---|
| Absolute neutrophil count | ≥0.5 and <1.5 × 109/l | <0.5 × 109/l |
| Thrombocyte count | ≥10 and <100 × 109/l | <10 × 109/l |
| CTC non-haematological toxicity (except for alopecia, nausea, vomiting) | CTC Grade 2 | CTC Grade 3 or 4 |
a Treatment with concomitant temozolomide can be continued when all of the following conditions are met: absolute neutrophil count ≥1.5 × 109/l; thrombocyte count ≥100 × 109/l; CTC non-haematological toxicity ≤Grade 1 (except for alopecia,
nausea, vomiting).
Four weeks after completing the temozolomide + RT concomitant phase, temozolomide is administered for up to 6 cycles of monotherapy treatment. Dose in Cycle 1 (monotherapy) is 150 mg/m² once daily for 5 days followed by 23 days without treatment. At the start of Cycle 2, the dose is escalated to 200 mg/m² if the CTC non-haematological toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea and vomiting), absolute neutrophil count (ANC) is ≥1.5 × 109/l, and the thrombocyte count is ≥100 × 109/l. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles. Once escalated, the dose remains at 200 mg/m² per day for the first 5 days of each subsequent cycle except if toxicity occurs. Dose reductions and discontinuations during the monotherapy phase should be applied according to Tables 2 and 3.
During treatment a complete blood count should be obtained on Day 22 (21 days after the first dose of temozolomide). The dose should be reduced or administration discontinued according to Table 3.
Table 2. Temozolomide dose levels for monotherapy treatment:
| Dose level | Temozolomide 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 |
Table 3. Temozolomide dose reduction or discontinuation during monotherapy treatment:
| Toxicity | Reduce temozolomide by 1 dose levela | Discontinue temozolomide |
|---|---|---|
| Absolute neutrophil count | <1.0 × 109/l | See footnote b |
| Thrombocyte count | <50 × 109/l | See footnote b |
| CTC non-haematological Toxicity (except for alopecia, nausea, vomiting) | CTC Grade 3 | CTC Grade 4b |
a Temozolomide dose levels are listed in Table 2.
b Temozolomide is to be discontinued if:
The appropriate dose of temozolomide should be infused intravenously using a pump over a period of 90 minutes.
Oral
75 - 200 mg per m² of body surface area (BSA)
From 75 To 200 mg per m² of body surface area (BSA) once every day
Temozolomide is administered in combination with focal radiotherapy (concomitant phase) followed by up to 6 cycles of temozolomide (TMZ) monotherapy (monotherapy phase).
Temozolomide is administered orally at a dose of 75 mg/m² daily for 42 days concomitant with focal radiotherapy (60 Gy administered in 30 fractions). No dose reductions are recommended, but delay or discontinuation of temozolomide administration should be decided weekly according to haematological and non-haematological toxicity criteria. Temozolomide administration can be continued throughout the 42 day concomitant period (up to 49 days) if all of the following conditions are met:
During treatment a complete blood count should be obtained weekly. Temozolomide administration should be temporarily interrupted or permanently discontinued during the concomitant phase according to the haematological and non-haematological toxicity criteria as noted in Table 1.
Table 1. Temozolomide dosing interruption or discontinuation during concomitant radiotherapy and temozolomide:
| Toxicity | Temozolomide interruptiona | Temozolomide discontinuation |
|---|---|---|
| Absolute neutrophil count | ≥0.5 and <1.5 × 109/l | <0.5 × 109/l |
| Thrombocyte count | ≥10 and <100 × 109/l | <10 × 109/l |
| CTC non-haematological toxicity (except for alopecia, nausea, vomiting) | CTC Grade 2 | CTC Grade 3 or 4 |
a Treatment with concomitant temozolomide can be continued when all of the following conditions are met: absolute neutrophil count ≥1.5 × 109/l; thrombocyte count ≥100 × 109/l; CTC non-haematological toxicity ≤Grade 1 (except for alopecia,
nausea, vomiting).
Four weeks after completing the temozolomide + RT concomitant phase, temozolomide is administered for up to 6 cycles of monotherapy treatment. Dose in Cycle 1 (monotherapy) is 150 mg/m² once daily for 5 days followed by 23 days without treatment. At the start of Cycle 2, the dose is escalated to 200 mg/m² if the CTC non-haematological toxicity for Cycle 1 is Grade ≤2 (except for alopecia, nausea and vomiting), absolute neutrophil count (ANC) is ≥1.5 × 109/l, and the thrombocyte count is ≥100 × 109/l. If the dose was not escalated at Cycle 2, escalation should not be done in subsequent cycles. Once escalated, the dose remains at 200 mg/m² per day for the first 5 days of each subsequent cycle except if toxicity occurs. Dose reductions and discontinuations during the monotherapy phase should be applied according to Tables 2 and 3.
During treatment a complete blood count should be obtained on Day 22 (21 days after the first dose of temozolomide). The dose should be reduced or administration discontinued according to Table 3.
Table 2. Temozolomide dose levels for monotherapy treatment:
| Dose level | Temozolomide 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 |
Table 3. Temozolomide dose reduction or discontinuation during monotherapy treatment:
| Toxicity | Reduce temozolomide by 1 dose levela | Discontinue temozolomide |
|---|---|---|
| Absolute neutrophil count | <1.0 × 109/l | See footnoteb |
| Thrombocyte count | <50 × 109/l | See footnoteb |
| CTC non-haematological Toxicity (except for alopecia, nausea, vomiting) | CTC Grade 3 | CTC Grade 4b |
a Temozolomide dose levels are listed in Table 2.
b Temozolomide is to be discontinued if:
The appropriate dose of temozolomide should be infused intravenously using a pump over a period of 90 minutes.
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