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Similarly, for the vascular damage score interlobular and smaller arteries were graded according to the following scheme: grade 0 – no wall thickening; grade 1, 2, 3 – mild, moderate and severe wall thickening, respectively; grade 4 – fibrinoid necrosis of the vascular wall.
If grade 2 or 3 diarrhoea or stomatitis occurred, the dose was reduced by 25 or 50%, respectively; grade 4 diarrhoea or stomatitis led to treatment withdrawal.
The incidence of nausea and vomiting was relatively low (grade 2 and 3 was reported for 29 (24%) and 12 (10%) patients, respectively, grade 4 for one patient).
According to these criteria, 10 and 19 patients were diagnosed as anaplastic oligodendrogliomas (AO) or astrocytomas (AA), respectively, (grade III) and 106 as glioblastomas (GBM, grade IV).
Toxicities probably related to the study drug included two episodes of, respectively, grade 1 and 2 sinusitis and four patients experiencing grade 1 headache.
Fatigue was the most common solicited general symptom, reported after 54.0% 89.8%and20.0%50.0%.0% of doses in the F4/AS01 and F4/WFI groups, respectively (grade 3 severity after 0 22.4% of doses in the F4/AS01 groups).
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Toxicities occurred as follows during treatment: grade 1 and grade 2 gastrointestinal (GI) toxicity in 14/91 (15.4%) and 2/91 patients (2.2%), respectively; grades 1, 2, and 3 genitourinary (GU) toxicity in 38/91 (41.8%), 6/91 (6.6%), and 1/91 patients (1.1%), respectively.
Anemia was common: 43.9% in arm A and 54.9% in arm B. Grades 1 4 leucopenia were 33.3% and 45.2% in arm A and B patients, respectively; grades 3 and 4 leucopenia were 12.3% and 2.6%, respectively, in arm A and 18.3% and 8.7%, respectively, in arm B (Table 2; statistically significant difference P value 0.017).
In conducting the investigation, three grades of Zn 22% Al were used; grades 1 and 2 contain 180 and 100 p.p.m. of impurities, respectively, whereas grade 3 is a high-purity grade containing 6 p.p.m. of impurities.
Only hypertension and proteinuria were more common in older patients when compared with younger patients (6.9% versus 4.2%, respectively, for grade ≥3 hypertension; 4.0% versus 1.5%, respectively, for grade ≥3 proteinuria); and grade ≥3 arterial/venous thromboembolism events occurred in 2.9% versus 3.3%, respectively.
Grade 3 events occurred in 8% and <1% of patients, respectively; no grade 4 events were observed.
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