Indications: Anaplastic astrocytoma: Treatment of refractory anaplastic astrocytoma (refractory to a regimen containing a nitrosourea and procarbazine). Glioblastoma multiforme: Treatment of newly-diagnosed glioblastoma multiforme (initially in combination with radiotherapy, then as maintenance treatment)

Cautions: Pneumocystis jiroveci pneumonia— for monitoring and prophylaxis requirements. monitor liver function before treatment initiation, after each treatment cycle and midway through 42-day treatment cycles— consider the balance of benefits and risks of treatment if results are abnormal at any point (fatal liver injury reported). monitor for myelodysplastic syndrome and secondary malignancies.

Note: This medication is in a class the Institute for Safe.

Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

CHILD under 3 years not recommended

Contra-indications: Hypersensitivity (eg, allergic reaction, anaphylaxis, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis) to temozolomide or any component of the formulation.

hypersensitivity to dacarbazine (both drugs are metabolized to MTIC)

Canadian labeling: Additional contraindications (not in U.S. labeling): Not recommended in patients with severe myelosuppression.

Side Effects: Note: With CNS malignancies, it may be difficult to distinguish between CNS adverse events caused by temozolomide versus the effects of progressive disease. >10%: Cardiovascular: Peripheral edema, Central nervous system: Fatigue, headache, seizure, hemiparesis, fever, dizziness, coordination abnormality, Dermatologic: Alopecia, rash, Gastrointestinal: Nausea, vomiting: constipation, anorexia, diarrhea, Hematologic: Lymphopenia (grades 3/4:, thrombocytopenia (grades 3/4: adults: 4% to 19%; children:, neutropenia (grades 3/4: adults: 8% to 14%; children:, leukopenia (grades 3/4: , Neuromuscular & skeletal: Weakness, Miscellaneous: Viral infection, Central nervous system: Amnesia, insomnia, somnolence, ataxia, paresis, anxiety, memory impairment, depression, confusion, Dermatologic: Pruritus, dry skin, radiation injury (2% maintenance phase after radiotherapy), erythema, Endocrine & metabolic: Hypercorticism, breast pain (females 6%) Gastrointestinal: Stomatitis, abdominal pain, dysphagia, taste perversion, weight gain, Genitourinary: Incontinence, urinary tract infection, urinary frequency, Hematologic: Anemia Neuromuscular & skeletal: Paresthesia, back pain, abnormal gait, arthralgia, myalgia, Ocular: Blurred vision, diplopia, vision abnormality (visual deficit/vision changes) Respiratory: Pharyngitis, upper respiratory tract infection, cough, sinusitis, dyspnea, Miscellaneous: Allergic reaction (Limited to important or life-threatening): Alkaline phosphatase increased, alveolitis, anaphylaxis, aplastic anemia, cholestasis, emotional lability, erythema multiforme, febrile neutropenia, flu-like syndrome, hallucination, hematoma, hemorrhage, hepatitis, hepatotoxicity, herpes simplex, herpes zoster, hyperbilirubinemia, hyperglycemia, hypokalemia, injection site reactions (erythema, irritation, pain, pruritus, swelling, warmth), interstitial pneumonia/pneumonitis, myelodysplastic syndrome, opportunistic infection (eg, PCP), oral candidiasis, pancytopenia (may be prolonged), peripheral neuropathy, petechiae, pneumonitis, pulmonary fibrosis, secondary malignancies (including myeloid leukemia), Stevens-Johnson syndrome, toxic epidermal necrolysis, transaminases increased.

Dose: Adult:

Note: Temozolomide is associated with a moderate emetic potential (Roila, 2010); antiemetics are recommended to prevent nausea and vomiting. Prior to dosing, ANC should be ≥1500/mm3 and platelets ≥100, 000/mm3. Anaplastic astrocytoma (refractory): Oral, IV: Initial dose 150 mg/m2 once daily for 5 consecutive days of a 28-day treatment cycle. If ANC ≥1500/mm3 and platelets ≥100, 000/mm3, on day 1 of subsequent cycles, may increase to 200 mg/m2 once daily for 5 consecutive days of a 28-day treatment cycle. May continue until disease progression.

Dosage modification for toxicity:

ANC <1000/mm3 or platelets <50, 000/mm3 on day 22 or day 29 (day 1 of next cycle): Postpone therapy until ANC

>1500/mm3 and platelets >100, 000/mm3. reduce dose by 50 mg/m2/day (but not below 100 mg/m2) for subsequent cycle. ANC 1000-1500/mm3 or platelets 50, 000-100, 000/mm3 on day 22 or day 29 (day 1 of next cycle): Postpone therapy until ANC >1500/mm3 and platelets

>100, 000/mm3; maintain initial dose Glioblastoma multiforme (newly diagnosed, high-grade glioma): Oral, IV: Concomitant phase: 75 mg/m2/day for 42 days with focal radiotherapy (60 Gy administered in 30 fractions). Note: PCP prophylaxis is required during concomitant

phase and should continue in patients who develop lymphocytopenia until lymphocyte recovery to ≤grade 1. Obtain weekly CBC. Continue at 75 mg/m2/day throughout the 42-day concomitant phase (up to 49 days) as long as ANC ≥1500/mm3, platelet count ≥100,

000/mm3, and non hematologic toxicity ≤grade 1 (excludes alopecia, nausea/vomiting) Dosage modification for toxicity: ANC ≥500/mm3 but <1500/mm3 or platelet count ≥10, 000/mm3 but <100, 000/mm3 or grade 2 non hematologic toxicity (excludes alopecia, nausea/vomiting): Interrupt therapy ANC <500/mm3 or platelet count <10, 000/mm3 or grade 3/4 non hematologic toxicity (excludes alopecia, nausea/vomiting): Discontinue therapy. Maintenance phase (consists of 6 treatment cycles): Begin 4 weeks after concomitant phase completion.

Note: Each subsequent cycle is 28 days (consisting of 5 days of drug treatment followed by 23 days without treatment). Draw CBC within 48 hours of day 22; hold next cycle and do weekly CBC until ANC >1500/mm3 and platelet count >100, 000/mm3; dosing modification should be based on lowest blood counts and worst non hematologic toxicity during the previous cycle.

Cycle 1: 150 mg/m2 once daily for 5 days of a 28-day treatment cycle. Cycles 2-6: May increase to 200 mg/m2 once daily for 5 days. repeat every 28 days (if ANC

≥1500/mm3, platelets ≥100, 000/mm3 and non

hematologic toxicities for cycle 1 are ≤grade 2 [excludes alopecia, nausea/vomiting]).

Note: If dose was not escalated at the onset of cycle 2, do not increase for cycles 3-6) Dosage modification (during maintenance phase) for toxicity: ANC <1000/mm3, platelet count <50, 000/mm3, or grade 3 non hematologic toxicity (excludes alopecia, nausea/vomiting) during previous cycle: Decrease dose by 1 dose level (by 50 mg/m2/day for 5 days), unless dose has already been lowered to 100 mg/m2/day, then discontinue therapy.

If dose reduction <100 mg/m2/day is required or grade 4 non hematologic toxicity (excludes alopecia, nausea/vomiting), or if the same grade 3 non hematologic toxicity occurs after dose reduction: Discontinue therapy Glioblastoma multiforme (recurrent glioma): Canadian labeling (unlabeled use in the U.S.): 200 mg/m2/day for 5 days every 28 days; if previously treated with chemotherapy, initiate at 150 mg/m2/day for 5 days every 28 days and increase to 200 mg/m2/day for 5 days every 28 days with cycle 2 if no hematologic toxicity (Brada, 2001; Yung, 2000) Cutaneous T-cell lymphoma, advanced (mycosis fungoides [MF] and Sézary syndrome [SS]; unlabeled use): Oral: 200 mg/m2 once daily for 5 days every 28 days for up to 1 year (Querfeld, 2011)

Ewing’s sarcoma, recurrent or progressive (unlabeled use): Oral: 100 mg/m2/dose days 1 to 5 every 21 days (in combination with irinotecan) (Casey, 2009). Additional data may be necessary to further define the role of temozolomide in this condition Melanoma, advanced or metastatic (unlabeled use): Oral: 200 mg/m2/day for 5 days every 28 days (for up to 12 cycles). For subsequent cycles reduce dose to 75% of the original dose for grade 3/4 hematologic toxicity and reduce the dose to 50% of the original dose for grade 3/4 non hematologic toxicity (Middleton, 2000). Neuroendocrine tumors, advanced.