rocytoma:
Tables 8 and 9 show the incidence of adverse reactions in the 158 patients in the anaplastic astrocytoma study for whom data are available. In the absence of a control group, it is not clear in many cases whether these reactions should be attributed to temozolomide or the patients' underlying conditions, but nausea, vomiting, fatigue, and hematologic effects appear to be clearly drug-related. The most frequently occurring adverse reactions were nausea, vomiting, headache, and fatigue. The adverse reactions were usually NCI Common Toxicity Criteria (CTC) Grade 1 or 2 (mild to moderate in severity) and were self-limiting, with nausea and vomiting readily controlled with antiemetics. The incidence of severe nausea and vomiting (CTC Grade 3 or 4) was 10% and 6%, respectively. Myelosuppression (thrombocytopenia and neutropenia) was the dose-limiting adverse reaction. It usually occurred within the first few cycles of therapy and was not cumulative.
Myelosuppression occurred late in the treatment cycle and returned to normal, on average, within 14 days of nadir counts. The median nadirs occurred at 26 days for platelets (range: 21–40 days) and 28 days for neutrophils (range: 1–44 days). Only 14% (22/158) of patients had a neutrophil nadir and 20% (32/158) of patients had a platelet nadir, which may have delayed the start of the next cycle. Less than 10% of patients required hospitalization, blood transfusion, or discontinuation of therapy due to myelosuppression.
In clinical trial experience with 110 to 111 women and 169 to 174 men (depending on measurements), there were higher rates of Grade 4 neutropenia (ANC less than 500 cells/µL) and thrombocytopenia (less than 20,000 cells/µL) in women than men in the first cycle of therapy (12% vs. 5% and 9% vs. 3%, respectively).
In the entire safety database for which hematologic data exist (N=932), 7% (4/61) and 9.5% (6/63) of patients over age 70 experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. For patients less than or equal to age 70, 7% (62/871) and 5.5% (48/879) experienced Grade 4 neutropenia or thrombocytopenia in the first cycle, respectively. Pancytopenia, leukopenia, and anemia have also been reported.
TABLE 8: Adverse Reactions in the Anaplastic Astrocytoma Trial in Adults (≥5%) No. (%) of TEMODAR Patients (N=158)
All Reactions Grade 3/4
Any Adverse Reaction 153 (97) 79 (50)
* Blurred vision; visual deficit; vision changes; vision troubles
Body as a Whole
Headache 65 (41) 10 (6)
Fatigue 54 (34) 7 (4)
Asthenia 20 (13) 9 (6)
Fever 21 (13) 3 (2)
Back pain 12 (8) 4 (3)
Cardiovascular
Edema peripheral 17 (11) 1 (1)
Central and Peripheral Nervous System
Convulsions 36 (23) 8 (5)
Hemiparesis 29 (18) 10 (6)
Dizziness 19 (12) 1 (1)
Coordination abnormal 17 (11) 2 (1)
Amnesia 16 (10) 6 (4)
Insomnia 16 (10) 0
Paresthesia 15 (9) 1 (1)
Somnolence 15 (9) 5 (3)
Paresis 13 (8) 4 (3)
Urinary incontinence 13 (8) 3 (2)
Ataxia 12 (8) 3 (2)
Dysphasia 11 (7) 1 (1)
Convulsions local 9 (6) 0
Gait abnormal 9 (6) 1 (1)
Confusion 8 (5) 0
Endocrine
Adrenal hypercorticism 13 (8) 0
Gastrointestinal System
Nausea 84 (53) 16 (10)
Vomiting 66 (42) 10 (6)
Constipation 52 (33) 1 (1)
Diarrhea 25 (16) 3 (2)
Abdominal pain 14 (9) 2 (1)
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