Prospective non-interventional BELOVA/BGOG-ov16 study on safety of frontline bevacizumab in elderly patients with FIGO stage IV ovarian cancer: a study of the Belgian and Luxembourg Gynaecological Oncology Group.

OBJECTIVE: Because elderly patients with ovarian cancer are underrepresented in randomized studies, this study aimed to expand our knowledge on the safety and effectiveness of frontline treatment with bevacizumab in combination with standard carboplatin and paclitaxel chemotherapy in patients aged 70 years and older with a diagnosis of Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer in routine clinical practice in Belgium. METHODS: Patients aged 70 years and older with FIGO stage IV ovarian cancer were included in a multicenter, non-interventional prospective studyto evaluate the safety and effectiveness of treatment with bevacizumab in combination with frontline carboplatin and paclitaxel chemotherapy. Comprehensive geriatric assessments were performed at baseline and during treatment. RESULTS: The most frequently reported adverse events for bevacizumab were hypertension (55%), epistaxis (32%) and proteinuria (21%). The Kaplan-Meier estimate of progression-free survival was 14.5 months. The results of the comprehensive geriatric assessments during treatment indicated a slight improvement in the geriatric eight health status screening tool score for general health status and the mini-nutritional assessment score for nutritional status. The median change from baseline score was close to zero for the instruments measuring independency, activity of daily living and instrumental activities of daily living, and for the mobility-tiredness test measuring self-perceived fatigue. CONCLUSIONS: No new safety signals were registered in this study in patients aged 70 years and older treated with bevacizumab and frontline carboplatin and paclitaxel for FIGO stage IV ovarian cancer. Elderly patients should not be excluded from treatment for advanced ovarian cancer based on age alone. EU PAS REGISTER: ENCEPP/SDPP/13849. CLINICALTRIALSGOV IDENTIFIER: NCT02393898.

Silkworm and spider silk electrospinning: a review.

Issues of fossil fuel and plastic pollution are shifting public demand toward biopolymer-based textiles. For instance, silk, which has been traditionally used during at least 5 milleniums in China, is re-emerging in research and industry with the development of high-tech spinning methods. Various arthropods, e.g. insects and arachnids, produce silky proteinic fiber of unique properties such as resistance, elasticity, stickiness and toughness, that show huge potential for biomaterial applications. Compared to synthetic analogs, silk presents advantages of low density, degradability and versatility. Electrospinning allows the creation of nonwoven mats whose pore size and structure show unprecedented characteristics at the nanometric scale, versus classical weaving methods or modern techniques such as melt blowing. Electrospinning has recently allowed to produce silk scaffolds, with applications in regenerative medicine, drug delivery, depollution and filtration. Here we review silk production by the spinning apparatus of the silkworm Bombyx mori and the spiders Aranea diadematus and Nephila Clavipes. We present the biotechnological procedures to get silk proteins, and the preparation of a spinning dope for electrospinning. We discuss silk's mechanical properties in mats obtained from pure polymer dope and multi-composites. This review highlights the similarity between two very different yarn spinning techniques: biological and electrospinning processes.

Investigation about the Effect of Manufacturing Parameters on the Mechanical Behaviour of Natural Fibre Nonwovens Reinforced Thermoplastic Composites.

To date, nonwoven fabrics made with natural fibres and thermoplastic commingled fibres have been extensively used in the composite industry for a wide variety of applications. This paper presents an innovative study about the effect of the manufacturing parameters on the mechanical behaviour of flax/PP nonwoven reinforced composites. The mechanical properties of nonwoven fabric reinforced composites are related directly to the ones of dry nonwoven reinforcements, which depend strongly on the nonwoven manufacturing parameters, such as the needle-punching and areal densities. Consequently, the influence of these manufacturing parameters will be analysed through the tensile and flexural properties. The results demonstrated that the more areal density the nonwoven fabric has, the more the mechanical behaviour can be tested for composites. By contrast, it has a complex influence on needle-punching density on the load-strain and bending behaviours at the composite scale.

Application of Flame-Retardant Double-Layered Shell Microcapsules to Nonwoven Polyester.

A microencapsulated flame retardant was used in order to produce a flame retardant nonwoven substrate. Melamine-formaldehyde polymer-shell microcapsules, containing Afflamit® PLF 280 (resorcinol bis(diphenyl phosphate)) as the core substance, were coated by an outer thermoplastic wall (polystyrene (PS) or poly(methyl methacrylate)), before being applied to a core/sheet-type bi-component PET/co-PET spunbond nonwoven substrate using impregnation. The outer wall of the microcapsules was heated to the softening temperature of the thermoplastic shell in order to be bonded onto the textile fibres. The thermal stability of the microcapsules was examined using thermogravimetric analysis. The textile samples were observed with a scanning electron microscope, and the flame retardancy performance was evaluated using the NF P92-504 standard. The results show that the composition of the outer polymeric shell affected the thermal stability of the microcapsules, since the particles with a PS shell are more stable. Furthermore, the microcapsules were more located at the nonwoven surface without affecting the thickness of the samples. Based on the results of the NF P92-504 test, the flame spread rate was relatively low for all of the tested formulations. Only the formulation with a low content of PS was classified M2 while the others were M3.

Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer.

BACKGROUND: This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer. METHODS: Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival. RESULTS: The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016). CONCLUSIONS: Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.

Patient outcome in the Belgian medical need program on bevacizumab for recurrent glioblastoma.

Bevacizumab (BEV) has demonstrated anti-tumor activity in patients with recurrent glioblastoma (rGB). Given the unmet need for active therapeutic options in rGB patients, a medical need program was initiated by the Belgian competent authorities. Between November 2010 and February 2013, a total of 313 patients with rGB initiated treatment with BEV administered at a dose of 10 mg/kg every 2 weeks. All patients had failed prior treatment with at least radiation therapy and temozolomide and the majority of patients (70 %) were treated with corticosteroids at baseline. Patients received a median of 6 BEV administrations (range 1-53). Overall, BEV was well tolerated. During BEV treatment the WHO-Performance Score (WHO-PS) improved in 59 patients (19 %) and stabilized for at least 6 weeks in an additional 139 (44 %) patients. Corticosteroid treatment could be stopped in 16 % or reduced in dose in 32 % of patients. The best objective tumor response rate using RANO criteria (investigator's assessment) was 3.5 % CR, 22 % PR, 38 % SD and 37 % PD. The median and 6-month PFS were 13 weeks (95 % CI 12.7-14) and 27.3 % (95 % CI 22.3-32.5), median and 6-month OS rates were 26 weeks (23-29) and 52 % (46.4-58.6), respectively. WHO-PS (0-1 vs. 2-3) and baseline steroid use were significantly correlated with PFS and OS. Our observations support the use of BEV as a monotherapy for patients with rGB who have no alternative treatment options. Optimal benefit from BEV treatment is likely to be obtained when treatment is initiated before the performance status deteriorates to two or less.

Weekly docetaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Single-agent docetaxel, administered as a 3-weekly infusion has encouraging clinical activity against squamous cell carcinoma of the head and neck (SCCHN). Weekly administration of docetaxel is feasible and showed a favorable toxicity profile in phase I studies. We studied a weekly docetaxel regimen in heavily pretreated patients with head and neck cancer. PATIENTS AND METHODS: A total of 30 patients with proven metastatic or recurrent SCCHN were treated with docetaxel 36 mg/m weekly for 6 weeks in an 8-week schedule. Dexamethasone 20 mg or methylprednisolone 32 mg was administered 12 and 3 hours before docetaxel. No prophylactic antibiotics or growth factors were given. The primary end point was objective response rate and the secondary end points included time to progression and overall survival. RESULTS: Patients received a median of 6 administrations (range, 1-27). A partial response was documented in 2 patients (6.7%). The disease control rate defined the percentage of patients with responding or stable disease was 33.3%. The median progression-free survival was 7.4 weeks (95% confidence interval, 5.5-9.3 weeks) and the median overall survival was 17.9 weeks (95% confidence interval, 10.1-25.6 weeks). There were no episodes of grade 4 neutropenia, thrombocytopenia, or nonhematological toxicity. CONCLUSIONS: Weekly docetaxel at a dose of 36 mg/m has a mild to moderate toxicity profile in SCCHN patients. However, the response rate in predominantly pretreated patients is low and the overall survival is short.