EFFICIENCY AND TOXICITY OF IFOSFAMIDE, CISPLATIN AND DOXORUBICIN IN THE TREATMENT OF CHILDHOOD HEPATOBLASTOMA

The Cooperative German Paediatric Liver Tumour Study HB89 was conceive d to evaluate the efficiency and toxicity of ifosfamide, cisplatin and doxorubicin (IPA) in children with resectable and non-resectable hepa toblastoma (HB) and to determine late sequelae including tubular nephr opathy of tumour treatment. The study also assessed the results of a s urgical strategy, which adapts the procedure at the initial operation to the tumour's extension in the liver. The relationship of the tumour s' histological differentiation to response to chemotherapy was also e xamined. Patients with a HB restricted to one liver lobe underwent pri mary resection. Larger tumours were initially treated with IPA chemoth erapy and resected at second-look surgery. All patients received IPA a djuvantly after tumour resection. The IPA regimen consisted of ifosfam ide 3.5 g/m(2) (over 72 h days 1-3), cisplatin 100 mg/m(2) (over 5 day s 4-8) and doxorubicin 60 mg/m(2) (over 48 h, days 9-10). Median follo w-up of survivors was 64 months (range 28-82). Long-term disease-free survival (DFS) was for stage I: 21/21; stage II: 3/6; stage III: 28/38 ; and stage IV: 2/7 (overall 75%). Severe surgical complications occur red in 15% (4/27) of primary and 21% (8/38) of secondary resections wi th no lethality. 44/45 stage III/IV HB displayed PR after two IPA cour ses. Drug resistance developed in 8/12 tumours after four or five chem otherapy courses. Acute toxicity was observed in 34/242 (14%) IPA cour ses. Late sequelae were found in 7/54 (13%) of survivors, and subclini cal renal tubulopathy occurred in 7/41 investigated patients (17%). De spite a more favourable prognosis in pure fetal and predominantly feta l histology, statistical analysis revealed no relationship between tum our differentiation and response to chemotherapy. In conclusion, IPA c hemotherapy in combination with delayed surgery was highly effective i n the treatment of HB. (C) 1997 Published by Elsevier Science Ltd.