Temozolomide

TEMOZOLOMIDE- temozolomide capsule
Accord Healthcare Inc.

1 INDICATIONS AND USAGE

1.1 Newly Diagnosed Glioblastoma

Temozolomide capsule is indicated for the treatment of adult patients with newly diagnosed glioblastoma concomitantly with radiotherapy and then as maintenance treatment.

1.2 Refractory Anaplastic Astrocytoma

Temozolomide capsule is indicated for the treatment of adult patients with refractory anaplastic astrocytoma who have experienced disease progression on a drug regimen containing nitrosourea and procarbazine.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage and Dosage Modifications for Newly Diagnosed Glioblastoma

Administer temozolomide capsules either orally or intravenously once daily for 42 consecutive days during the concomitant phase with focal radiotherapy and then once daily on Days 1 to 5 of each 28-day cycle for 6 cycles during the maintenance phase.

Provide Pneumocystis pneumonia (PCP) prophylaxis during the concomitant phase and continue in patients who develop lymphocytopenia until resolution to grade 1 or less [see Warnings and Precautions (5.3)] .

Concomitant Phase

The recommended dosage of temozolomide capsules is 75 mg/m ² orally once daily for 42 days (up to 49 days) concomitant with focal radiotherapy (60 Gy administered in 30 fractions). Focal radiotherapy includes the tumor bed or resection site with a 2-to 3-cm margin.

Obtain a complete blood count weekly. No dose reductions are recommended during the concomitant phase. The recommended dosage modifications during the concomitant phase are provided in Table 1.

TABLE 1: Temozolomide Dosage Modifications During Concomitant Phase

Adverse Reaction	Interruption	Discontinuation
Absolute Neutrophil Count	Withhold temozolomide if ANC is greater than or equal to 0.5 x 10 9 /L and less than 1.5 x 10 9 /L. Resume temozolomide when ANC is greater than or equal to 1.5 x 10 9 /L.	Discontinue temozolomide if platelet count is less than 0.5 x 10 9 /L.
Platelet Count	Withhold temozolomide if platelet count is greater than or equal to 10 x 10 9 /L and less than 100 x 10 9 /L. Resume temozolomide when platelet count is greater than or equal to 100 x 10 9 /L.	Discontinue temozolomide if platelet count is less than 10 x 10 9 /L.
Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting)	Withhold temozolomide if Grade 2 adverse reaction occurs. Resume temozolomide when resolution to Grade 1 or less.	Discontinue temozolomide if Grade 3 or 4 adverse reaction occurs.

Maintenance Phase

Beginning 4 weeks after Concomitant Phase completion, administer temozolomide either orally or intravenously once daily on Days 1 to 5 of each 28-day cycle for 6 cycles. The recommended dosage of temozolomide is as follows:

• Cycle 1: 150 mg/m ² per day
• Cycles 2 to 6: May increase to 200 mg/m ² per day if the following conditions are met before starting cycle 2. If the dose was not escalated at the onset of Cycle 2, do not increase the dose for Cycles 3 to 6.
  • Non-hematologic toxicity is Grade 2 or less (except for alopecia, nausea, vomiting)
  • ANC is greater than or equal to 1.5 x 10 ⁹ /L and
  • Platelet count is greater than or equal to 100 x 10 ⁹ /L.

Obtain a complete blood count on Day 22 and then weekly until the ANC is above 1.5 x 10 ⁹ /L and the platelet count is above 100 x 10 ⁹ /L. Do not start the next cycle until the ANC and platelet count exceed these levels.

The recommended dosage modifications during the maintenance phase are provided in Table 2. If Temozolomide is withheld, reduce the dose for the next cycle by 50 mg/m ² per day. Permanently discontinue Temozolomide in patients who are unable to tolerate a dose of 100 mg/m ² per day.

TABLE 2: Temozolomide Dosage Modifications During Maintenance Treatment

Toxicity	Interruption and Dose Reduction	Discontinuation
Absolute Neutrophil Count	Withhold temozolomide if ANC less than 1 x 10 9 /L. When ANC is above 1.5 x 10 9 /L, resume temozolomide at reduced dose for the next cycle.	Unable to tolerate a dose of 100 mg/m 2 per day.
Platelet Count	Withhold temozolomide if platelet less than 50 x 10 9 /L. When platelet count is above 100 x 10 9 /L, resume temozolomide at reduced dose for the next cycle.	Unable to tolerate a dose of 100 mg/m 2 per day.
Non-hematological Adverse Reaction (except for alopecia, nausea, vomiting)	Withhold temozolomide if Grade 3 adverse reaction. When resolved to grade 1 or less, resume temozolomide at reduced dose for the next cycle.	Recurrent Grade 3 after dose reduction. Grade 4 Unable to tolerate a dose of 100 mg/m 2 per day.