ABSTRACT
BACKGROUND: The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers. METHODS: COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled. RESULTS: The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3-69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children. CONCLUSION: COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasms/drug therapy , Registries , Administration, Metronomic , Adolescent , Adult , Celecoxib , Child , Child, Preschool , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Etoposide/administration & dosage , Europe , Feasibility Studies , Female , Fenofibrate/administration & dosage , Humans , Infant , Isotretinoin/administration & dosage , Male , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Temozolomide , Vitamin D/administration & dosage , Young AdultABSTRACT
OBJECTIVES: The aim of this study is to evaluate the significance of nasal bone as a marker for trisomy 21 in the group of women that underwent invasive procedures in our center at 11 to 14 weeks' gestation. METHODS: The data of 181 women who had undergone the invasive procedures were evaluated for the presence or absence of nasal bone retrospectively and were correlated with fetal karyotype. RESULTS: A successful view of the fetal profile was obtained in 135 fetuses. The nasal bone was absent in 5 of 8 fetuses with trisomy 21 and in 3 of 4 fetuses with trisomy 18. In the group of chromosomally normal fetuses the nasal bone was absent in 4 of the 123 cases. The false positive rate of our screening program dropped from 4.5% to 2.5% after the introduction of the nasal bone evaluation into our risk calculation model for trisomy 21. CONCLUSION: Nasal bone evaluation improved the detection of trisomy 21 in the first trimester in our screening program and reduced the need for invasive procedures in our department. Absence of the nasal bone showed a sensitivity of 63% for a 5% false positive rate for trisomy 21 in our study. It is rarely observed in chromosomally normal fetuses (2.5%). An appropriate training is mandatory in order to achieve acceptable results.
