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Targeted therapies (TT) are used in pediatric patients based on the data from adult literature. In 2008, the French Sarcoma Study Group and the Bone Tumor Group (Groupe Sarcome Français-Groupe d'étude des Tumeurs Osseuses) opened Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes (OUTC'S), a national registry of targeted off-label sarcomas therapies. All patients registered in the OUTC'S database and treated in pediatric oncology units were included in this analysis. We describe TTs using off-label and off clinical trial practices for children with sarcoma. We analyzed TT tolerability and efficacy for 34 patients with osteosarcoma (n = 20), Ewing sarcoma (n = 9), clear cell sarcoma (n = 1), synovialsarcoma (n = 1), epithelioid sarcoma (n = 1), myofibroblastic tumor (n = 1), and desmoid tumor (n = 1) who were registered from six pediatric centers. In total, 38 different TT courses were administered. The median age was 15 years (5-23) and 18.5 years (7-27) at diagnosis and at the time of starting TT, respectively. The decision to initiate TT was taken in a multidisciplinary board in 92% of the cases. TT included sirolimus (alone or in association with other treatments), sunitinib, sorafenib, cetuximab, imatinib, and crizotinib. The median duration of treatment was 109 days (21-515). Of the 34 patients, 6 had a partial response with a median response duration of 3.72 months (2.08-30.8) and 10 had a stabilization of the disease with a median duration of 3.63 months (0.75- 16.89). In our cohort, overall survival and progression-free survival were 8.68months (95% confidence interval [CI]: 5.85-11.50) and 3.29 months (95% CI: 2.69-3.88), respectively. Grades 3 and 4 toxicities were reported for seven patients (26%) and were most commonly hematological. Patients under 15 years of age did not show severe toxicity. Hence, TT is an acceptable therapeutic option for refractory pediatric sarcomas. It is very important to continue collecting data and develop phase I/II protocols. [ABSTRACT FROM AUTHOR]

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age approximately 13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m(-2)/150 mg m(-2) day(-1), 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1-7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin-temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m(-2) cisplatin and 150 mg m(-2) x 5 temozolomide in heavily treated, and 200 mg m(-2) x 5 temozolomide in less-heavily pretreated children. [ABSTRACT FROM AUTHOR]

Purpose: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to peform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. Patients and methods One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150 mg/m[SUP2] × 7 days, followed by Doxorubicin, 35 mg/m[SUP2] i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. Results After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (≥ 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. Conclusion Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy. [ABSTRACT FROM AUTHOR]

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[sup2]). 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. [ABSTRACT FROM AUTHOR]

Studies the disease osteosarcoma, a common malignant bone tumor found in children and young adults. Use of technetium bone scanning to detect tumor growth; Treatment of children according to a multicenter trial.

Summary: Angiogenesis is crucial for the growth of cancer. As such, it has become an established target in fighting cancer. Metronomic chemotherapy—the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration at close regular intervals, with no prolonged drug-free breaks—is a potential novel approach to controlling advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has the property of killing resistant cancer cells while significantly reducing undesirable toxic side effects. We review the data regarding the use of metronomic chemotherapy in children with cancer and discuss its potential uses and limits. [Copyright &y& Elsevier]