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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.British Journal of Cancer (2006) 95, 571–580. doi:10.1038/sj.bjc.6603288 www.bjcancer.com Published online 1 August 2006 [ABSTRACT FROM AUTHOR]

This report describes a single-centre study with temozolomide (TMZ) (200 mg m(-2) day(-1) x 5 per cycle of 28 days) in children with (recurrent) high-grade glioma. Magnetic resonance imaging was performed every two cycles. In all, 20 patients were treated between 1998 and 2001 after the UKCCSG/SFOP TMZ phase II trial. All patients had measurable disease. Totally, 15 patients had a relapse after surgery+/-radiotherapy+/-chemotherapy. Overall, five patients received TMZ after surgery or biopsy, awaiting radiotherapy. There were one clinically malignant grade II glioma, 11 grade III and eight grade IV gliomas. Seven tumours had oligodendroglial features. Mean age at start of TMZ was 12.0 years (range 3-20.5 years). In total, eight patients had >8 cycles (range 3-30). One VGPR (currently in CR after surgery), three PRs (with a PFS of 4, 4 and 11 months, respectively) and one MR (PFS 14 months) were observed. Three out of five responses occurred after >4 courses. The overall response rate was 20%. Median progression-free survival (PFS) was 2.0 months (range 3 weeks-34+ months). PFS rate was 20% after 6 months. Median overall survival (OS) was 10 months. Nine patients showed a clinical improvement. Three patients vomitted shortly after TMZ administration, eight patients (13 cycles) experienced grade III/IV thrombocytopenia, occurring predominantly during the fourth week of the first two cycles. Five patients experienced neutropenia, and three patients febrile neutropenia. TMZ is a well-tolerated ambulatory treatment for children with malignant glial tumours. This drug warrants further study in these highly chemoresistant tumours and should be studied either as upfront therapy or in combination therapy. [ABSTRACT FROM AUTHOR]

We analysed the clinical features and outcome of young patients with non-Ewing's flat bone sarcoma treated during the era of contemporary chemotherapy. The characteristics and outcome of 25 patients (15 males and 10 females) with primary or radiation-related flat bone sarcoma treated in the Pediatrics Department at the Institut Gustave Roussy from 1981 to 1999 were reviewed. In all, 20 patients had osteosarcoma, four chondrosarcoma and one malignant fibrous histiocytoma. The age at diagnosis ranged from 2 to 23 years (median, 15 years). Nine tumours were located in the craniofacial bones, 11 in the pelvis and five in flat bones at other sites. Four patients had metastatic disease at diagnosis. Radiation-associated flat bone osteosarcoma was diagnosed in 10 out of 25 cases. The projected overall survival and event-free survival (EFS) rates at 5 years were 45.1 and 34.3% for all the 25 patients. The EFS rate of patients with second bone sarcoma was similar to that of patients with de novo flat bone sarcoma (P=0.1). The aim of treatment was curative for 24 patients, 23 of whom were treated with intensive chemotherapy regimens and 19 with surgery. Significant adverse prognostic factors on survival included incomplete surgical resection (P=0.001) and use of regimens without pre- and postoperative chemotherapy (P=0.007). Nine of the 25 patients were treated with pre- and postoperative chemotherapy and complete surgical resection. Among them, eight are alive with no disease. Radical surgical resection is the overriding prognostic factor for flat bone sarcomas in young patients. Nevertheless, our results suggest a more favourable outcome since the advent of intensive chemotherapy.British Journal of Cancer (2004) 90, 613-619. doi:10.1038/sj.bjc.6601564 www.bjcancer.com [ABSTRACT FROM AUTHOR]

In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities in the molecular events following Fas and TNF-alpha receptor engagement, we report that U937 cells, genetically engineered to constitutively produce hGH, were made more sensitive to TNF-alpha-induced apoptosis than parental cells. This was due to overproduction of the antioxidant glutathione, which decreased the nuclear factor (NF)-kappaB activity known to control the expression of survival genes. These findings were confirmed in vivo, in nude mice bearing U937 tumours coinjected with recombinant hGH and the NF-kappaB -inducing anticancer drug daunorubicin, to avoid the in vivo toxicity of TNF-alpha. This study therefore highlights one of the various properties of hGH that may have potential clinical implications. [ABSTRACT FROM AUTHOR]

Background: Although survival from childhood cancer has increased, little is known on the long-term impact of treatment late effects on occupational attainment or work ability., Methods: A total of 3512 five-year survivors treated before the age of 19 years in 10 French cancer centres between 1948 and 2000 were identified. Educational level, employment status and occupational class of survivors were assessed by a self-reported questionnaire. These outcome measures were compared with sex-age rates recorded in the French population, using indirect standardisation. Paternal occupational class was also considered to control for the role of survivors' socioeconomic background on their achievement. Multivariable analyses were conducted to explore clinical characteristics associated with the outcomes., Results: A total of 2406 survivors responded to the questionnaire and survivors aged below 25 years were included in the current analysis. Compared with national statistics adjusted on age and sex, male survivors were more likely to be college graduates (39.2% vs 30.9% expected; P<0.001). This higher achievement was not observed either for leukaemia or central nervous system (CNS) tumour survivors. Health-related unemployment was higher for survivors of CNS tumour (28.1% vs 4.3%; P<0.001) but not for survivors of other diagnoses. Survivors of non-CNS childhood cancer had a similar or a higher occupational class than expected., Conclusions: Survivors treated for CNS tumour or leukaemia, especially when treatment included cranial irradiation, might need support throughout their lifespan.