Metronomic Four-Drug Regimen Has Anti-tumor Activity in Pediatric Low-Grade Glioma; The Results of a Phase II Clinical Trial

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 has shown its efficacy in adult tumor types such as breast and ovarian cancer and has to some extent been studied in pediatrics.Objective: To assess the anti-tumor activity and toxicity of a four-drug metronomic regimen in relapsing/refractory pediatric brain tumors (BT) with progression-free survival (PFS) after two cycles as primary endpoint.Methods: Patients ≥4 to 25 years of age were included with progressing BT. Treatment consisted of an 8-week cycle of celecoxib, vinblastine, and cyclophosphamide alternating with methotrexate. Kepner and Chang two-steps model was used with 10 patients in the first stage. If stabilization was observed in ≥2 patients, 8 additional patients were recruited. Assessment was according WHO criteria with central radiology review.Results: Twenty-nine patients (27 evaluable) were included in two groups: ependymoma (group 1, N = 8), and miscellaneous BT (group 2): 3 medulloblastoma (MB), 5 high grade glioma (HGG), 11 low grade glioma (LGG), 2 other BT. After first stage, recruitment for ependymoma was closed [one patient had stable disease (SD) for 4 months]. Cohort 2 was opened for second stage since 1 HGG and 3 LGG patients had SD after two cycles. Recruitment was limited to LGG for the second stage and 2 partial responses (PR), 6 SD and 2 progressive disease (PD) were observed after two cycles. Of these patients with LGG, median age was 10 years, nine patients received vinblastine previously. Median number of cycles was 6.8 (range: 1–12). Treatment was interrupted in five patients for grade 3/4 toxicity.Conclusion: This regimen is active in patients with LGG, even if patients had previously received vinblastine. Toxicity is acceptable.Trial Registration: This study was registered under clinicaltrials.gov – NCT01285817; EUDRACT nr: 2010-021792-81

Off-label use of targeted therapies in osteosarcomas: data from the French registry OUTC'S (Observatoire de l'Utilisation des Thérapies Ciblées dans les Sarcomes):

BACKGROUND: The objective of this study is to explore the off-label use of targeted therapies (TTs) for patients with osteosarcoma registered within the French Sarcoma Group--Bone Tumor Study Group (GSF-GETO) national registry. METHODS: All patients with an osteosarcoma, registered between January 1, 2009 and July 15, 2013 were analyzed. RESULTS: Twenty-nine patients with refractory relapsed osteosarcomas received 33 treatment lines of TTs. The median age at the beginning of treatment was 19 years (range 9-72). The median number of previous lines of chemotherapy was 3 (range 1-8). Before inclusion, 3 patients were in second complete remission, 26 were in progression for metastatic relapse. Twenty-three patients received sirolimus (in combination with cyclophosphamide for 18); 5, sunitinib; 4, sorafenib; and one, pazopanib. Stable disease was observed for 45.5% of patients (95% Confidence Interval (CI) [20-52.8]). The median Progression-Free Survival (PFS) was 3 months (95% CI [2-5.4]) for patients treated by sirolimus and 1.8 months (95% CI [1.3-2.8]) for patients receiving multi-targeted tyrosine kinase inhibitors; 6-month PFS 15%. The median Overall Survival (OS) was 6.8 months (95% CI [4.7-12.1]), and one-year OS was 24%. In a multivariate analysis, PFS was superior for patients receiving sirolimus compared to other TTs (Hazard Ratio (HR) = 2.7, 95% CI [1.05-7.1]). No toxic death was reported. Grade 3 and 4 toxicities were observed in 27 and 6% of cases respectively. CONCLUSION: Off-label TTs, especially sirolimus, reported benefit in the treatment of refractory osteosarcomas with an acceptable toxicity profile, including in pediatric population

X-ray diffraction setup for breast tissue characterization: Experimental validation on beef phantoms

International audienc

Pilot evaluation of physical and psychological effects of a physical trek programme including a dog sledding expedition in children and teenagers with cancer

International audienceAim of the study: To evaluate the feasibility and to measure the effects of a six-week-long adapted physical activity programme (APAP), including 5 days of intense dog sledding, on the physical and psychological health of children and adolescents treated for cancer. Methods: Eleven children and teenagers (4 girls, 7 boys; mean age 14.3 ± 2.9 years) participated in this monocentric pilot programme of adapted physical activities from February 2013 to March 2013. Seven were still on treatment. The programme lasted 6 weeks. A series of physical tests and psychological questionnaires were carried out before and after the programme. Results: All children and teenagers completed the full programme. An improvement in all physical and psychological parameters was observed. Statistically significant differences were observed for global self-esteem (6.2 ± 2.1 to 7.7 ± 1.8; p = 0.02), perceived sport competence (5.3 ± 3.2 to 7.4 ± 2; p = 0.02) and perceived physical strength (5.6 ± 2.5 to 7.1 ± 1.8; p = 0.001). Regarding physical tests, the physical training led to statistically significant improvement for sit-ups (13.8 ± 2.6 to 21.75 ± 5.4; p = 0.01), muscle tone (76 ± 23.7 to 100 ± 22.9; p = 0.01), and resting heart rate (96.1 ± 3.2 to 91.6 ± 4.5; p = 0.03). Conclusion: This programme is feasible in children and adolescents even during their oncologic treatment. During the 6-week programme, children and adolescents improved their physical and psychological health, and the putative benefits of the APAP are discussed. A larger randomised trial started in 2014

Pilot evaluation of physical and psychological effects of a physical trek programme including a dog sledding expedition in children and teenagers with cancer

AIM OF THE STUDY: To evaluate the feasibility and to measure the effects of a six-week-long adapted physical activity programme (APAP), including 5 days of intense dog sledding, on the physical and psychological health of children and adolescents treated for cancer. METHODS: Eleven children and teenagers (4 girls, 7 boys; mean age 14.3 ± 2.9 years) participated in this monocentric pilot programme of adapted physical activities from February 2013 to March 2013. Seven were still on treatment. The programme lasted 6 weeks. A series of physical tests and psychological questionnaires were carried out before and after the programme. RESULTS: All children and teenagers completed the full programme. An improvement in all physical and psychological parameters was observed. Statistically significant differences were observed for global self-esteem (6.2 ± 2.1 to 7.7 ± 1.8; p = 0.02), perceived sport competence (5.3 ± 3.2 to 7.4 ± 2; p = 0.02) and perceived physical strength (5.6 ± 2.5 to 7.1 ± 1.8; p = 0.001). Regarding physical tests, the physical training led to statistically significant improvement for sit-ups (13.8 ± 2.6 to 21.75 ± 5.4; p = 0.01), muscle tone (76 ± 23.7 to 100 ± 22.9; p = 0.01), and resting heart rate (96.1 ± 3.2 to 91.6 ± 4.5; p = 0.03). CONCLUSION: This programme is feasible in children and adolescents even during their oncologic treatment. During the 6-week programme, children and adolescents improved their physical and psychological health, and the putative benefits of the APAP are discussed. A larger randomised trial started in 2014