[Analysis of selected undesirable effects of cytostatic drugs in treatment of the central nervous system tumours in children. Preliminary report].

Introduction: During treatment of children with brain tumours there is a large risk of occurrence of side effects related to the narrow therapeutic range of cytostatic drugs and irradiation of the central nervous system.

Aim: Determination of the patients' risk of undesirable effects and determination of intensification of myelosuppression and hepatocellular damage during treatment of central nervous system tumours, depending on the used therapeutic protocol and the time of chemotherapy.

Material And Methods: The investigated group consisted of 17 patients (5 girls, 12 boys) aged 1.5-16 yrs, treated for primary brain tumour. The patients were treated according to different protocols. Protocol I (vincristine, etoposide, carboplatin, cyclophosphamide, ifosfamide and cisplatin) in 4 children with medulloblastoma and with PNET. Protocol II (etoposide, ifosfamide, adriamycin) in 4 children with glioblastoma multiformae, astrocytoma anaplasticum and ependymoma. Protocol III (carboplatin and vincristine) in 3 children with medulloblastoma, ependymoma and glioblastoma multiformae. Protocol IV (vincristine and carboplatin) in 4 children with astrocytoma fibrillare and astrocytoma pilocyticum. 10 patients were given radiotherapy. Frequency of occurrence and intensification of undesirable effects were valuated according to the WHO classification after each cycle of chemotherapy (average 8 cycles) during the whole treatment period (average 8 months): 1. Leucopenia (mm3): 0 grade [gr] (>4.000), 1 gr. (3.000-3.900), 2 gr. (2.000-2.900), 3 gr. (1.000-1.900), 4gr. ( 100000), 1 gr. (75-99000), 2 gr. (50-74000), 3 gr. (25-49000), 4 gr. (<25000) 3. Anaemia (g/dl): 0 gr. (N), 1 gr. (>10), 2 gr. (8-10), 3 gr. (6.5-7.9), 4 gr. (<6.5) 4. Hepatocellular damage (GPT, GOT/bilirubin): 0 gr. (N/N), 1 gr. (2.5xN/-), 2 gr. (2.6-5xN/1.5xN), 3 gr. (5.1-20xN/1.5-3xN), 4 gr. (>20xN/>3xN).

Results: In patients treated in accordance with the therapeutic protocols there was no appearance or exacerbation of undesirable side effects. During receiving adriamycin mild hyperbilirubinemia (R=0.53; p<0.05 bilirubin 1 degree) occurred statistically significantly more often. Correlation between usage of temodal and the activity of hepatic enzymes was noticed, meeting the requirements of 1st degree of toxicity according to WHO rates (R-0.66). Consequently, after the usage of temodal, more frequent abnormalities in liver function were shown. During treatment with cyclophosphamide, iphosphamide, etoposide, carboplatin, lomustine and vincristine, complications such as myelotoxicity and hepatotoxicity were not more frequent by statistical significance methods.

Conclusions: Current results of treatment of central nervous system tumours in children showed, that patients tolerated cytostatic therapy relatively well. The observed undesirable effects were abnormal liver enzyme activity and bilirubin levels, higher after adriamycin and temodal therapy. Due to the small group of patients, these results are of preliminary significance. In future, a more in depth analysis of early and late effects of oncological treatment in children with cns tumours is needed.