Metabolic functions of the liver during chemotherapy in children with acute lymphoblastic leukemia.

OBJECTIVE: The purpose of the present work was estimation of liver function using the phenazone test and commonly used biochemical tests in children with acute lymphoblastic leukemia (ALL) during anticancer treatment. METHODS: Observations were carried out in the same 21 patients with ALL before the beginning of chemotherapy, after Protocol I and after Protocol M of the antileukemic treatment carried out according to the program BFM 86. RESULTS: The applied chemotherapy inhibited phenazone elimination. Both phenazone half-life and metabolic clearance rate were significantly different in patients after treatment with anticancer drugs, especially with high-dose of methotrexate (MTX), from those in patients before the beginning of chemotherapy (p < 0.001). Moreover, after MTX administration transaminases activity and serum bilirubin concentration were significantly higher than before treatment (p < 0.05). CONCLUSION: Our results showed that in children with acute lymphoblastic leukemia, anticancer chemotherapy decreased liver metabolic capacity. Particularly, high-dose methotrexate treatment altered the elimination of phenazone by inhibiting the activity of hepatic mixed function oxidase system. This change may lead to an increase in toxicity of active drugs which are metabolized by this enzyme system. In addition, altered activity of liver metabolic function can impair transformation of prodrugs to active forms. It should be considered in selection of individual drug dosages. The objective estimation of the type and degree of liver dysfunction can only be achieved by the combination of a quantitative phenazone dynamic test and static biochemical tests.

[Results of treatment of osteosarcoma in children according to the SFOP-94 protocol in the experience of the Polish Paediatric Solid Tumour Study Group]. / Wyniki leczenia dzieci chorych na miesaka kosciopochodnego wedlug protokolu SFOP-94 w materiale Polskiej Grupy Pediatry Cznej ds. Leczenia Guzów Litych.

Between April 1994 and December 1999, 34 children aged from 5 to 20 years (23 females and 11 males) suffering from osteosarcoma, were treated according to the SFOP-94 protocol. The primary preoperative chemotherapy consists of adriamycin and high-dose methotrexate administration. There were 28 patients with non-metastatic tumours of the extremities and 6 children presented disseminated disease with pulmonary metastases. The primary localization included femur - 20 patients, tibia - 9 patients and humerus - 5 patients. In 26 patients limb-salvage surgery was applied. The programme of chemotherapy was changed in 4 children because of toxicity of methotrexate (1 patient) and progression of disease (3 patients). 26 out of 34 (76,5 %) children are alive including 24 out of 28 patients with localized disease. EFS calculated according to Kaplan-Meier analysis was 60 % at 67 months.

[The analysis of failures in therapy of osteosarcoma in children treated according to SFOP-94 protocol in the studies of Polish pediatric solid tumors treatment group]. / Analiza niepowodzen leczenia miesaka kosciopochodnego u dzieci wedlug protokolu SFOP-94 w materiale Polskiej Pediatrycznej Grupy ds. Leczenia Guzów Litych.

Between December 1989 and April 1998 twenty eight children aged from 5 to 20 years (18 female and 10 male) suffering from osteosarcoma were treated according to the OS-SFOP-94 protocol. Twenty four patients presented with localized tumor of extremities and four with pulmonary metastases. The majority of primary tumors exceeded 150 ml of volume. The primary preoperative chemotherapy consisted of adriamycin (70 mg/m2 every four weeks) and high-dose methotrexate (12 g/m2 every week). In 20 patients limb-salvage surgery was applied, in three children--amputation and in one child tibia resection with genu arthrodesis was applied. Five of 28 patients died, one because of treatment related infection, 2 non-responders with metastatic osteosarcoma due to progressive disease, and one because of local relapse with pulmonary metastasis non-responding to therapy, one because of treatment refusal. Twenty one from 25 children are alive from 5 to 51 months. Event frae survival of children with localized disease calculated according to Kaplan-Meier analysis was 64.17% in the 51st month. The main cause of failure in the treatment of osteosarcoma in children is primary and secondary progression of disease. The toleration and results of treatment for osteosarcoma in children according to the OS-SFOP-94 is satisfactory.

[The evaluation of neoplasm markers in the diagnosis and treatment of germ cell tumors in children]. / Ocena roli markerów nowotworowych w rozpoznawaniu i monitorowaniu leczenia guzów germinalnych u dzieci.

In the Department of Paediatric Hematology and Oncology (University School of Medicine in Wroclaw) 25 patients, 1 to 19 years old, 8 boys and 17 girls, suffering from germ cell tumors were treated from June 1989 to August 1998. In the course of the treatment both surgery, chemotherapy and radiotherapy were used. The level of oncological markers: alpha-fetoprotein (AFP), lactic dehydrogenase (LDH), carcinoembryonal antigen (CEA), beta-choriongonadotropin (beta-HCG) and CA 125 was examined at the beginning, during the therapy, and at the end of the treatment. Increased levels of oncological markers were found: AFP in 17 children, LDH in 10 children, CEA in 3 children, beta-HCG in 3 children and CA 125 in 2 children. In all cases the level of AFP was decreasing during the therapy. Normal levels of AFP and LDH were observed in children with complete remission. The use of AFP in diagnostics and monitoring of germ cell tumors was proved.