Time filter

Source Type

Couec M.-L.,Nantes University Hospital Center | Andre N.,Service dOncologie Pediatrique | Thebaud E.,Center Oscar Lambret | Minckes O.,Service dOncologie Pediatrique | And 6 more authors.
Pediatric Blood and Cancer | Year: 2012

Background: Bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, has proven efficacy in some adult tumors; it is now proposed as a new therapeutic strategy for refractory or recurrent brain tumors in some children, either alone or combinated. Procedure: We retrospectively analyzed 28 children who received bevacizumab on a compassionate basis for refractory or recurrent brain tumors between June 2007 and August 2010 in 7 French centers. Among them, 12 had high-grade gliomas, 7 low-grade gliomas, 4 ependymomas, 2 primitive neurectodermal tumors, 3 neuroglial tumors. The median age at start of bevacizumab was 11.0 years. Bevacizumab was administered at 5-10mg/kg every 2 weeks, with concomitant chemotherapy for 27 patients. Results: Bevacizumab was used in combination with irinotecan in 27 patients. Bevacizumab-related toxicity was mild. Toxicities reported were grade I-II hypertension (n=4), proteinuria (n=1), lymphopenia (n=2), wound healing delay (n=2). Whereas tumor reduction could be observed in 6:7 patients with low-grade gliomas, no efficacy could be documented in patients with high-grade glioma, nor PNET nor ependymoma. Conclusion: Bevacizumab-related acute toxicity appears to be low in children, even in combination with irinotecan. Further prospective trials are required to confirm the hypothetical efficacy of bevacizumab and to assess the risk of long-term toxicity especially in the youngest children. © 2012 Wiley Periodicals, Inc.


PubMed | Service de neurochirurgie, CLCC Paul Strauss, Service doncologie pediatrique and University of Strasbourg
Type: Journal Article | Journal: Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique | Year: 2016

Retrospective analysis of the results of 52 children irradiated for a medulloblastoma.Between 1974 and 2012, 52 children with an average age of 6 years and a half (11 months-17 years and a half) were treated with surgery then with radiotherapy at the Comprehensive Cancer Centre of Strasbourg (France). For 44 children, the treatment consisted of a chemotherapy.After a mean follow-up of 106.6 months (7-446 months), 13 relapses and 24 deaths were observed. Overall survival at 5 years and 10 years were 62% and 57%, respectively. Disease-free survival at 5 years and 10 years were 80% and 63%, respectively. Univariate analysis found the following adverse prognostic factors: the existence of a postoperative residue, the positivity of the cerebrospinal fluid, the metastatic status and medulloblastoma of high-risk. Positivity of the cerebrospinal fluid remains a negative factor in multivariate analysis.These results confirm the survival rate obtained by a conventional approach (surgery then irradiation). Insufficiency of results and rarity of medulloblastoma require the establishment of international protocols.


Andre N.,Service dHematologie et Oncologie Pediatrique | Andre N.,Metronomics Global Health Initiative | Abed S.,Service dHematologie et Oncologie Pediatrique | Orbach D.,University Pierre and Marie Curie | And 7 more authors.
Oncotarget | Year: 2011

Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. MC is gaining interest as an alternative strategy to fight resistant cancer. Objective: to assess the safety of 4 drug MC regimen in pediatric patients with refractory or relapsing various tumors types. Setting: From November 2008 to December 2010, in three academic pediatric oncology centers, 16 children (median age 12 years old; range 5.5-20) were included in this pilot study. This treatment was proposed to children with refractory disease for whom no further effective treatments were available. Most frequent diagnosis were medulloblastoma/cerebral PNET (5) osteosarcoma (5), and one case each of nephroblastoma, high grade glioma, Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma and kidney rhabdoid tumour. The MC regimen consisted in cycles of 56 days (8 weeks) with weekly vinblastine 3 mg/mï¿1/2 (week 1-7), daily cyclophosphamide 30 mg/mï¿1/2 (days 1-21), and twice weekly methotrexate 10 mg/mï¿1/2 (days 21-42), and daily celecoxib 100 mg to 400 mg twice daily (days1-56) followed by a 2-weeks chemotherapy break. Adverse events were determined through laboratory analysis and investigator observations. Results: One objective response was observed in a patient with Hodgkin lymphoma, and 4 patients experienced disease stabilization and continued their treatment for 3 cycles (24 weeks) or more. At last follow-up, 7 patients (43%) are alive including 1 still undergoing treatment. During the overall 36 cycles of treatments received by patients, 4 grade IV toxicities and 24 grade III toxicities were observed in 11 cycles in only 10 different patients. Conclusion: The metronomic regimen we report here was well tolerated and associated with disease stabilization. This regimen is currently being evaluated in a national multicenter phase II study. © André et al.


Pasquier E.,University of New South Wales | Kavallaris M.,University of New South Wales | Andre N.,Service dOncologie Pediatrique
Nature Reviews Clinical Oncology | Year: 2010

Tumor angiogenesis is recognized as a major therapeutic target in the fight against cancer. The key involvement of angiogenesis in tumor growth and metastasis has started to redefine chemotherapy and new protocols have emerged. Metronomic chemotherapy, which is intended to prevent tumor angiogenesis, is based on more frequent and low-dose drug administrations compared with conventional chemotherapy. The potential of metronomic chemotherapy was revealed in animal models a decade ago and the efficacy of this approach has been confirmed in the clinic. In the past 5 years, multiple clinical trials have investigated the safety and efficacy of metronomic chemotherapy in a variety of human cancers. While the results have been variable, clinical studies have shown that these new treatment protocols represent an interesting alternative for either primary systemic therapy or maintenance therapy. We review the latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients. Accumulating evidence suggests that the efficacy of such treatment may not only rely on anti-angiogenic activity. Potential new mechanisms of action, such as restoration of anticancer immune response and induction of tumor dormancy are discussed. Finally, we highlight the research efforts that need to be made to facilitate the optimal development of metronomic chemotherapy. © 2010 Macmillan Publishers Limited.


Malignant extraconal orbital tumors are very rare during childhood and must be referred as soon as possible to a highly specialized center to be managed by a multidisciplinary team. They are often referred on an emergency basis. Both diagnosis and treatment must be undertaken as soon as possible. The course of these malignant tumors can be acute and can jeopardize the function of the eye or be life-threatening, especially in the event of metastatic locations. Extra-axial proptosis is by far the most frequent revealing symptom. Local and general examinations are of utmost importance. Sometimes diagnosis should be clear with the association of an orbital tumor and deterioration of the general health status favoring metastatic disease. Most metastatic neuroblastomas present such clinical symptoms in young children. Today both CT and MRI are highly valuable in assessing the diagnosis and starting the management of these tumors. Biopsy is mandatory to confirm the diagnosis. It can be reinforced by molecular biology. Among the primitive tumors, soft tissue sarcomas, especially rhabdomyosarcomas, are the most frequent. The diagnosis is suggested when the onset of the disease is acute and the course is rapid. Most respond to neoadjuvant chemotherapy. In the event of a residual tumor, local treatment is indicated so that surgery and/or radiotherapy are used as second-line treatment. Prognosis is closely related to histology. It can be satisfactory (Langerhans' cell histiocytosis, lymphoma, meningioma, infantile fibrosarcoma) or poor (metastatic tumor, rhabdoid tumor). © 2010 Elsevier Masson SAS.


Fousseyni T.,Service dOncologie Pediatrique | Diawara M.,Service dOncologie Pediatrique | Pasquier E.,University of New South Wales | Andre N.,Service dOncologie Pediatrique
Journal of Pediatric Hematology/Oncology | Year: 2011

Background: Metronomic chemotherapy (MC) is defined as the frequent administration of chemotherapy at doses below the maximal tolerated dose and with no prolonged drug-free break. As off-patent chemotherapeutic drugs can be used and given the low toxicity profile of this approach, MC seems to be well adapted to low-income countries. Objective: The aim of this study was to assess the efficacy and safety of a vincristine/cyclophosphamide/methotrexate MC regimen given to children with refractory cancer of various tumor types. Methods: This prospective, pilot, single-center study evaluated the use of MC with a first cycle consisting of weekly vincristine (1.5 mg/m) on days 1, 8, 15, and 22, daily cyclophosphamide (25 mg/m) on days 1 to 21, and twice weekly methotrexate (15 mg/m) on days 21 to 42, followed by a 1-week break. For the following cycles, vincristine was administered only at weeks 1 and 5 of the cycle. This treatment was proposed to children with refractory cancer following treatments with the standard protocols available in our institution and to patients who were not eligible for the protocol. Adverse events were determined through laboratory analyses and investigator observations. Results: From November 2008 to December 2009, 12 children (median age, 3.7 y; range, 2 to 7 y) were included. The most frequent diagnoses were Wilms tumors (6) and retinoblastoma (5). No objective response was observed, but 7 patients experienced disease stabilization (58%) and continued their treatment for 15 to 24 weeks. After a median follow-up of 39 weeks, 6 patients (50%) were alive. Most importantly, in 3 patients (25%), disease remained stable for at least 6 months after completion of treatment. One grade 4 anemia was observed in 1 patient and 1 grade 4 nonfebrile neutropenia in 1 patient. No other grade 3 or 4 toxicities were noted. Conclusion: The MC regimen that we report here was well tolerated and was associated with disease stabilization. Most importantly, stabilization could be maintained for over 6 additional months after completion of treatment in 3 patients. The potential of MC in children and young adults in low-income countries warrants further studies. Copyright © 2011 by Lippincott Williams & Wilkins.


Andre N.,Service dOncologie Pediatrique
Current cancer drug targets | Year: 2010

Tumor angiogenesis, i.e. the development of neovascularisation in and around solid tumors, plays a key role in the local and distant growth of cancer and anti-angiogenic treatments are now established strategies to treat cancer patients. Specific inhibitors of angiogenesis such as bevacizumab or receptor tyrosine kinase inhibitors targeting VEGFR or PDGFR are now in clinical trials and are being increasingly validated for the treatment of poor prognostic cancers. Other anti-angiogenic strategies such as cilengitide or metronomic chemotherapy (low-dose anti-angiogenic chemotherapy) have been developed to treat certain types of adult cancer. In children, the clinical potential of anti-angiogenic approach is still in an early stage of investigation. This review will focus on the role of angiogenesis in pediatric solid tumors and will describe the pre-clinical and clinical experience with several anti-angiogenic compounds as a potential treatment for children with cancer.


Kashanskiy S.V.,The Workers Lab | Andre N.,Service dOncologie Pediatrique | Andre N.,French Institute of Health and Medical Research
Bulletin du Cancer | Year: 2010

Paediatric mesothelioma is a very rare entity. We report here epidemiologic data from 489 cases reported in international medical literature. A better knowledge about this entity is mandatory to improve its management. ©John Libbey Eurotext.


PubMed | Service danathomopathologie, Service doncologie pediatrique and Service de chirurgie pediatrique
Type: Journal Article | Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | Year: 2016

Inflammatory myofibroblastic tumors (IMT) are rare benign tumors, most commonly arising in the lungs and urinary bladder. Many etiologic factors are suspected in their development, but none have been formally demonstrated. Conventional treatment for bladder IMT is complete surgical resection by partial cystectomy or transurethral resection. We report the case of an 8-year-old girl with documented bladder IMT that resolved completely after antibiotic therapy.


PubMed | British Petroleum, Service dophtalmologie, Service doncologie pediatrique and Laboratoire danatomie et cytologie pathologiques
Type: Journal Article | Journal: Journal francais d'ophtalmologie | Year: 2016

Describe the macroscopic and microscopic profiles of retinoblastoma (RB) in Senegal and correlate histological criteria with progression to establish severity factors.We realized a retrospective study over 10 years (January 2005-December 2014). Only patients (n=67) who underwent histological analysis of the enucleation specimen (n=68) were followed until the end of the study.The tumor measured an average of 3.8cm (2/4.5). Endophytic tumor development was observed in 55 cases (80.8%), exophytic in 6 cases (8.9%) and mixed in 7 cases (10.3%). Retinal detachment was present in 13 cases (19.2%). The RB was well differentiated in 11 cases (16.2%), moderately differentiated in 31 cases (45.6%) and undifferentiated in 26 cases. Optic nerve (ON) invasion was present in 18 cases (26.5%). The tumor was extraretinal in 37 cases (54.4%). The anterior chamber was invaded in 6 cases (8.8%). The global survival at 2 years was 84% and 70% at 5 years. On multivariate analysis, well differentiated tumors and stage pT1 were associated with remission. Retrolaminar ON invasion, massive choroidal invasion and stage pT3 were risk factors for recurrence. Poor tumor differentiation, invasion of the ON resection margin, tumor invasion through the sclera, and stage pT4 were predictive of death.The pathologist is a principal actor in the management of RB because his account guide the post-surgical management strategy.

Loading Service dOncologie Pediatrique collaborators
Loading Service dOncologie Pediatrique collaborators