these levels. Dose reductions during the next cycle should be based on the lowest blood counts and worst nonhematologic toxicity during the previous cycle. Dose reductions or discontinuations during the maintenance phase should be applied according to Tables 2 and 3.
TABLE 2: Temozolomide Dose Levels for Maintenance Treatment Dose Level 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 Maintenance Treatment Toxicity Reduce TMZ by 1 Dose Level* Discontinue TMZ
TMZ=temozolomide; CTC=Common Toxicity Criteria.
TMZ dose levels are listed in Table 2.
TMZ is to be discontinued if dose reduction to <100 mg/m2 is required or if the same Grade 3 nonhematological toxicity (except for alopecia, nausea, vomiting) recurs after dose reduction.
Absolute Neutrophil Count <1.0 × 109/L See footnote †
Platelet Count <50 × 109/L See footnote †
CTC Nonhematological Toxicity
(except for alopecia, nausea, vomiting) CTC Grade 3 CTC Grade 4†
Patients with Refractory Anaplastic Astrocytoma:
For adults the initial dose is 150 mg/m2 once daily for 5 consecutive days per 28-day treatment cycle. For adult patients, if both the nadir and day of dosing (Day 29, Day 1 of next cycle) ANC are ≥1.5 × 109/L (1500/µL) and both the nadir and Day 29, Day 1 of next cycle platelet counts are ≥100 × 109/L (100,000/µL), the TEMODAR dose may be increased to 200 mg/m2/day for 5 consecutive days per 28-day treatment cycle. During treatment, a complete blood count should be obtained on Day 22 (21 days after the first dose) or within 48 hours of that day, and weekly until the ANC is above 1.5 × 109/L (1500/µL) and the platelet count exceeds 100 × 109/L (100,000/µL). The next cycle of TEMODAR should not be started until the ANC and platelet count exceed these levels. If the ANC falls to <1.0 × 109/L (1000/µL) or the platelet count is <50 × 109/L (50,000/µL) during any cycle, the next cycle should be reduced by 50 mg/m2, but not below 100 mg/m2, the lowest recommended dose (see Table 4). TEMODAR therapy can be continued until disease progression. In the clinical trial, treatment could be continued for a maximum of 2 years, but the optimum duration of therapy is not known.
TABLE 4: Dosing Modification Table
TABLE 5: Daily Dose Calculations by Body Surface Area (BSA) Total BSA
(m2) 75 mg/m2
(mg daily) 150 mg/m2
(mg daily) 200 mg/m2
(mg daily)
1.0 75 150 200
1.1 82.5 165 220
1.2 90 180 240
1.3 97.5 195 260
1.4 105 210 280
1.5 112.5 225 300
1.6 120 240 320
1.7 127.5 255 340
1.8 135 270 360
1.9 142.5 285 380
2.0 150 300 400
2.1 157.5 315 420
2.2 165 330 440
2.3 172.5 345 460
2.4 180 360 480
2.5 187.5 375 500
TABLE 6: Suggested Capsule Combinations Based on Daily Dose in Adults Number of Daily Capsules by Strength (mg)
Total Daily Dose (mg) 250 mg 180 mg 140 mg 100 mg 20 mg 5 mg
75 0 0 0 0 3 3
82.5 0 0 0 0 4 0
90 0 0 0 0 4 2
97.5 0 0 0 1 0 0
105 0 0 0 1 0 1
112.5 0 0 0 1 0 2
120 0 0 0 1 1 0
127.5 0 0 0 1 1 1
135 0 0 0 1 1 3
142.5 0 0 1 0 0 0
150 0 0 1 0 0 2
157.5 0 0 1 0 1 0
165 0 0 1 0 1 1
172.5 0 0 1 0 1 2
180 0 1 0 0 0 0
187.5 0 1 0 0 0 1
195 0 1 0 0 0 3
200 0 1 0 0 1 0
210 0 0 0 2 0 2
220 0 0 0 2 1 0
225 0 0 0 2 1 1
240 0 0 1 1 0 0
255 1 0 0 0 0 1
260 1 0 0 0 0 2
270 1 0 0 0 1 0
280 0 0 2 0 0 0
285 0 0 2 |
