[Complications of hydroxyapatite orbital implants in children: a series of 105 cases]. / Complications des implants orbitaires en hydroxyapatite chez l'enfant. A propos de 105 cas.

PURPOSE: To describe the complications encountered using hydroxyapatite as an orbital implant in the pediatric population after enucleation, and try to define the risk factors for their occurrence. MATERIAL: and methods: Retrospective review of charts of children who underwent enucleation with placement of an hydroxyapatite implant between January 1991 and 1998. Complications and their type (conjunctival, extrusion, eyelids complications) have been specifically looked for. A statistical analysis trying to isolate the risks factors was performed. RESULTS: 105 implants have been used during this period with 26.7% of complications appearing during a median followup of 22 months. Extrusion of the implant was observed in 1.9% of the cases, a chronic conjunctival erosion in 15%, a conjunctival lesion without erosion in 4.75% and no eyelid lesion could be seen. Treatment (medical or surgical) achieved 75% good results. No risk factor could be found. CONCLUSION: Hydroxyapatite orbital implants were initially thought to have no or few complications. More recently, chronic erosions in particular were described. Little data exists on the pediatric population. Our series confirms that complications occur and that they are comparable to the adult population. Nevertheless the hydroxyapatite orbital implant seems better tolerated than other porous or non porous implants and warrants its use.

A phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumours.

Anthracyclines are widely used in paediatric oncology, but their use is limited by the risk of cumulative cardiac toxicity. Encapsulating anthracyclines in liposomes may reduce cardiac toxicity and possibly increase drug availability to tumours. A phase I study in paediatric patients was designed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) after a single course of liposomal daunorubicin, 'DaunoXome', as a 1 h infusion on day 1 of a 21 day cycle. Patients were stratified into two groups according to prior treatment: Group A (conventional) and group B (heavily pretreated patients). Dose limiting toxicity was expected to be haematological, and a two-step escalation was planned, with and without G-CSF support. Pharmacokinetic studies were carried out in parallel. In all, 48 patients aged from 1 to 18 years were treated. Dose limiting toxicity was neutropenia for both groups. Maximum tolerated dose was defined as 155 mg m(-2) for Group A and 100 mg m(-2) for Group B. The second phase with G-CSF was interrupted because of evidence of cumulative cardiac toxicity. Cardiac toxicity was reported in a total of 15 patients in this study. DaunoXome shares the early cardiotoxicity of conventional anthracyclines in paediatric oncology. This study has successfully defined a haematological MTD for DaunoXome, but the significance of this is limited given the concerns of delayed cardiac toxicity. The importance of longer-term follow-up in patients enrolled into phase I studies has been underestimated previously, and may lead to an under-recognition of important adverse events.

Phase I trial and pharmacological study of a 3-hour paclitaxel infusion in children with refractory solid tumours: a SFOP study.

The maximum tolerated dose of paclitaxel administered by 24-hour continuous infusion in children is known. Short infusion might offer equivalent antitumour efficacy and reduced haematological toxicity, without increasing the allergic risk. Our aims were to determine the maximum tolerated dose and the pharmacokinetics of paclitaxel in children when administered in 3-h infusion every 3 weeks. Patients older than 6 months, younger than 20 years with refractory malignant solid tumours were eligible when they satisfied standard haematological, renal, hepatic and cardiologic inclusion criteria with life expectancy exceeding 8 weeks. Paclitaxel was administered as a 3-hour infusion after premedication (dexamethasone, dexchlorpheniramine). Pharmacokinetic analysis and solvent assays (ethanol, cremophor) were performed during the first course. 20 courses were studied in 17 patients; 4 dosage levels were investigated (240 to 420 mg/m(2)). No dose-limiting haematological toxicity was observed. Severe acute neurological and allergic toxicity was encountered. One treatment-related death occurred just after the infusion at the highest dosage. Delayed peripheral neurotoxicity and moderate allergic reactions were also encountered. Pharmacokinetic analysis showed dose-dependent clearance of paclitaxel and elevated blood ethanol and Cremophor EL levels. Although no limiting haematological toxicity was reached, we do not recommend this paclitaxel schedule in children because of its acute neurological toxicity.