The sensitivity, specificity and accuracy of FDG-PET in the detection of recurrences from osseous sarcomas are high. On an examination-based analysis, FDG-PET had a not significantly lower sensitivity in comparison with conventional imaging. However, FDG-PET showed a small advantage in the detection of osseous and soft-tissue recurrences compared with conventional imaging.

Considering the low plasma concentrations and the persistence of toxicity in spite of dose reduction intermittent dosing schedules might be considered as an alternative to further dose reduction of ATRA in the treatment of APL especially in children, who might be at risk of ATRA-induced neurotoxicity.

The therapeutic benefit and side-effect profile of gemcitabine in adults with relapsed solid tumors is well known. So far, few data are available about its significance in pediatric relapsed solid tumors. To determine the efficacy and tolerability of gemcitabine in children, the drug was administered by intravenous short-term infusion over 30 min at a dose of 1200 mg/m2 weekly for 3 weeks as one cycle in children with relapsed solid tumor of embryonic or mesenchymal origin. From May 2003 to September 2004, 14 male and six female patients (2-23, median 15.8 years) were recruited for this prospective open-label phase II study (two-step Simon design). The patients suffered from rhabdomyosarcoma (n=8), Ewing's sarcoma (n=4), osteosarcoma (n=2), neuroblastoma (n=3), hepatoblastoma (n=2) and nephroblastoma (n=1). Median duration of therapy was 27.5 days (7-99), corresponding to 4.0 (2-11) infusions of gemcitabine. Two patients (neuroblastoma and Ewing) had stable disease documented for 69 and 70 days, whereas no objective responses were observed. In 34/94 administered infusions; doses had to be reduced or omitted for grade 3-4 hematotoxicity. Minimal activity was observed in this cohort of children with a wide spectrum of mesenchymal and embryonic tumors. Given the relatively low dose of gemcitabine administered, this study does not exclude the possibility of activity at higher doses. Secondly, the tolerability of gemcitabine in children was consistent with that expected in adults. For further studies in this population, we recommend the use of gemcitabine in combination with other agents.

No abstract

Our aim was to assess the pharmacokinetics of a low-dose schedule of paclitaxel in combination with radiation therapy in patients with brain tumors. Eighteen patients received 20-50 mg/m2 paclitaxel as a 1-h infusion 18-24 h before radiation with 2 Gy on 5 consecutive days. In total, 156 plasma samples from 13 patients and 38 urine samples from nine patients were collected and analyzed by a validated capillary electrophoresis method. Data analysis was done using NONMEM with a two-compartmental model and proportional error model. No signs of non-linearity in the pharmacokinetic parameters were observed in this dosing range. The median cumulative urinary excretion was 2.4% (range 0.86-7.72%) of the given dose. Plasma clearance was found to be 6.71 l/h+/-70% and central volume of distribution was 3.64 l+/-79% (population mean +/- interindividual variability, respectively). At the time of the radiation, i.e. 24 h after administration with the lowest dose of 20 mg/m2, the mean concentration of paclitaxel was 0.038 mg/l (0.045 microM) in plasma. We conclude that even with the lowest dose of 20 mg/m2 paclitaxel, plasma concentrations at the time of radiation are achieved which are radiosensitizing in vitro.