A phase II study of ifosfamide in children with recurrent solid tumours |
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Authors: | C. R. Pinkerton H. Rogers C. James A. Bowman P. R. H. Barbor O. B. Eden J. Pritchard |
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Affiliation: | (1) Department of Haematology & Oncology, The Hospital for Sick Children, Great Ormond Street, London, UK;(2) Department of Pharmacy, The Hospital for Sick Children, Great Ormond Street, London, UK;(3) Department of Clinical Pharmacology, Guys Hospital, London, UK;(4) Childrens Department, University Hospital, Nottingham, UK;(5) Department of Haematology, Royal Hospital for Sick Children, Edinburgh, UK |
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Abstract: | Summary Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2–3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children.Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 g/ml (median 80). The elimination half-life, at 2.5–5.2 h (median 3.2) was shorter than previously reported in adults.Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma. |
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