Academic literature on the topic '65.011.1 (477)'

AbstractTwo new isostructural minerals edtollite K2NaCu5Fe3+O2(AsO4)4 and alumoedtollite K2NaCu5AlO2(AsO4)4 have been found in the Arsenatnaya fumarole, Second scoria cone of the Northern Breakthrough of the Great Tolbachik Fissure Eruption, Tolbachik volcano, Kamchatka, Russia. They are associated with sylvite, tenorite, dmisokolovite, shchurovskyite, johillerite, bradaczekite, and orthoclase. Edtollite forms prismatic crystals up to 0.02 mm × 0.1 mm; alumoedtollite forms long-prismatic crystals up to 0.01 mm × 0.1 mm. Both minerals have a semi-metallic lustre. Edtollite is brown–black to black and alumoedtollite is bronze coloured. Dcalc. = 4.26 (edtollite) and 4.28 (alumoedtollite) g cm–3. In reflected light, both minerals are grey, with distinct anisotropy. Reflectance values [edtollite/alumoedtollite: R1–R2, % (λ, nm)] are: 8.3–8.2/8.7–7.7 (470); 7.7–7.4/8.3–7.4 (546); 7.1–6.9/8.3–7.4 (589); and 6.3–6.3/7.6–7.2 (650). Chemical data are: (edtollite/alumoedtollite, wt.%, electron-microprobe): Na2O 3.13/2.58, K2O 8.12/9.09, Rb2O 0.00/0.11, CaO 0.00/0.52, CuO 36.55/38.35, ZnO 0.46/0.00, Al2O3 0.00/3.48, Fe2O3 7.34/1.79, TiO2 0.27/0.00, As2O5 43.57/43.66, total 99.44/99.58. The empirical formulae, based on 18 O apfu, for edtollite is: K1.83Na1.07Cu4.88Zn0.06Fe3+0.98Ti0.04As4.03O18; and for alumoedtollite is: K2.02Rb0.01Na0.87Ca0.10Cu5.06Al0.72Fe3+0.24As3.99O18. Both minerals are triclinic, P$\bar{1}$; unit-cell parameters (edtollite/alumoedtollite) are: a = 5.1168(6)/5.0904(11), b = 9.1241(12)/9.0778(14), c = 9.6979(14)/9.6658(2) Å, α = 110.117(13)/110.334(17), β = 102.454(12)/102.461(19), γ = 92.852(11)/92.788(15)°, V = 411.32(9)/404.88(14) Å3 and Z = 1/1. The strongest reflections in the powder X-ray diffraction pattern [d,Å(I)(hkl)] are for edtollite: 8.79(92)(001), 7.63(41)(0$\bar{1}$1), 5.22(44)(011), 3.427(100)(012), 3.148(64)(0$\bar{1}$3), 2.851(65)($\bar{1}$03) and 2.551(40)($\bar{2}$01); and for alumoedtollite: 8.78(81)(001), 7.62(67)(0$\bar{1}$1), 3.418(100)(012), 3.147(52)(0$\bar{1}$3), 2.558(58)($\bar{1}$22), 2.544(65)($\bar{2}$01) and 2.528(52)($\bar{1}\bar{3}$2). The crystal structures [single-crystal X-ray diffraction, R = 0.0773 (edtollite) and 0.0826 (alumoedtollite); 1504 and 1046 unique reflections, respectively] represent a novel structure type. It is based upon a heteropolyhedral pseudo-framework with the column formed by Cu2+-centred octahedra and square pyramids, octahedra MO6 (M = Fe3+, Al3+ or Cu2+) and AsO4 tetrahedra as the main building unit. K+ and Na+ are located in wide and narrow channels, respectively. Edtollite is named after the Russian geologist and Arctic explorer Eduard Vasilievich Toll (1858–1902), alumoedtollite is its analogue with Al prevailing among trivalent cations.

AbstractObjectiveTo identify and compare the sociodemographic determinants of stunting, wasting and overweight among infants of urban and rural areas in the Ecuadorian highlands.DesignCross-sectional study.SettingNabon (rural) and Cuenca (urban) cantons, Azuay Province, Ecuador.SubjectsA total of 703 children aged 0–24 months and their caregivers (227 rural and 476 urban) recruited during the period from June to September 2008.ResultsStunting prevalence was significantly higher in the rural area (37·4 %v. 17·7 %;P< 0·001) while wasting (7·1 %) and overweight (17·1 %) prevalence were more similar between areas. Determinants of stunting for the pooled sample were male gender (OR = 1·43; 95 % CI 1·06, 1·92;P= 0·02), preterm delivery (OR = 1·65; 95 % CI 1·14, 2·38;P= 0·008), child's age (OR = 1·04; 95 % CI 1·01, 1·07;P= 0·011), maternal education (OR = 0·95; 95 % CI 0·92, 0·99;P= 0·025) and facility-based delivery (OR = 0·57; 95 % CI 0·45, 0·74;P< 0·001). The latter was also a determinant of overweight (OR = 0·39; 95 % CI 0·25, 0·62;P< 0·001). Rural determinants of stunting were maternal height (OR = 0·004; 95 % CI 0·00004, 0·39;P= 0·018), diarrhoea prevalence (OR = 2·18; 95 % CI 1·13, 4·21;P= 0·02), socio-economic status (OR = 0·79; 95 % CI 0·64, 0·98;P= 0·030) and child's age (OR = 1·07; 95 % CI 1·02, 1·11;P= 0·005). Urban determinants were: maternal BMI for stunting (OR = 0·91; 95 % CI 0·84, 0·99;P= 0·027), cough prevalence (OR = 0·57; 95 % CI 0·34, 0·96;P= 0·036) and facility-based delivery (OR = 0·25; 95 % CI 0·09, 0·73;P= 0·011) for overweight, and hygiene for wasting (OR = 0·57; 95 % CI 0·36, 0·89;P= 0·013).ConclusionsInfant malnutrition was associated with different sociodemographic determinants between urban and rural areas in the Ecuadorian highlands, a finding which contributes to prioritize the determinants to be assessed in nutritional interventions.

В статье рассмотрены физико-химические и органолептические показатели виноматериалов, выработанных из крымских и донских аборигенных сортов винограда, произрастающего в Ампелографической коллекции института «Магарач» в с. Вилино Бахчисарайского района и п. Гурзуф. Определены группы сортов, из которых получаются виноматериалы с хорошими пенистыми свойствами, оптимальным соотношением массовых концентраций винной и яблочной кислот, высокими дегустационными оценками. В частности, высокие показатели пенистых свойств (V более 800 см) определены в виноматериалах из сортов: Кокур белый 46-10-3, Кокур белый 46-10-6, Солнечная Долина 40, Солнечная Долина 71/1, Махроватчик. Средние показатели пенистых свойств (V 600-800 см) установлены в виноматериалах из сортов: Кокур белый (п. Гурзуф), Кокур белый, Кокур белый полурассеченный, Солнечнодолинский, Солнечная Долина 31а, Солнечная Долина 65, Цимлянский белый, Кефесия, Фирский ранний (с. Вилино). Массовая концентрация винной кислоты в виноматериалах варьировала в диапазоне 1,4-4,9 г/дм, яблочной кислоты - 0,1-3,2 г/дм, а лимонной - 0,1-1,2 г/дм. Более высокая массовая концентрация винной кислоты определена в виноматериалах Сых дане (4,9 г/дм), Мускат крымский (4,7 г/дм), Солнечнодолинский (4,2 г/дм), Буланый белый (4,2 г/дм), Солнечная Долина 65 (3,9 г/дм), Кокур белый (п. Гурзуф) - (3,6 г/дм), Кокур белый 46-10-3 (3,4 г/дм), Солнечная Долина 40 (3,3 г/дм), Махроватчик (3,3 г/дм), Капитан Яни кара (3,1 г/дм), а самая низкая - в виноматериале Цимлянский белый (1,4 г/дм). Показана перспективность использования для производства виноматериалов для игристых вин из винограда аборигенных сортов: Кокур белый, Кокур белый 46-10-3, Кокур белый 46-10-6, Солнечнодолинский, Солнечная Долина 40, Солнечная Долина 65, Сых дане, Сары пандас, Мускат крымский, Махроватчик, Кокур красный, Безымянный и Цимладар.The article discusses physico-chemical and organoleptic characteristics of base wines produced from Crimean and Don aboriginal grapevine cultivars grown in the Ampelographic collection of the Institute “Magarach” in Vilino village of Bakhchsarai region and in Gurzuf. Groups of cultivars which provide base wines with good sparkling properties, the optimum balance between mass concentrations of tartaric and malic acids and high tasting scores have been determined. In particular, high sparkling properties (V over 800 cm) were demonstrated by base wines from the following cultivars: ‘Kokur Belyi 46-10-3’, ‘Kokur Belyi 46-10-6’, ‘Solnechnaya Dolina 40’, ‘Solnechnaya Dolina 71/1’, ‘Mahrovatchik’. The average sparkling indexes (V 600-800 cm) were determined for base wines from the following varieties: ‘Kokur Belyi’ (v. Gurzuf), ‘Kokur Belyi’, ‘Kokur Belyi Polurassechenny’, ‘Solnechnodolinsky’, ‘Solnechnaya Dolina 31a’, ‘Solnechnaya Dolina 65’, ‘Tsimlyansky Belyi’, ‘Kefesiya’, ‘Firsky Rannyi’ (v. Vilino). Mass concentration of tartaric acid in the base wine varied between 1.4-4.9 g/dm, malic acid - 0.1-3.2 g/dm, and citric acid - 0.1-1.2 g/dm. A higher mass concentration of tartaric acid was defined for base wines from ‘Sykh Dane’ (4.9 g/dm), ‘Muscat Krymskyi’ (4.7 g/dm), ‘Solnechnodolinsky’ (4.2 g/dm), ‘Bulany Belyi’ (4.2 g/dm), ‘Solnechnaya Dolina’ 65 (3.9 g/dm), ‘Kokur Belyi’ (v. Gurzuf) - (3.6 g/dm), ‘Kokur Belyi 46-10-3’ (3.4 g/dm), ‘Solnechnaya Dolina 40’ (3.3 g/dm), ‘Mahrovatchik’ (3.3 g/dm), ‘Captain Yani Kara’ (3.1 g/dm); the lowest in ‘Tsimlyansky Belyi’ grapes (1.4 g/dm). The potential of using indigenous varieties of grapevines for the production of base wine for sparkling wines was demonstrated for the following cultivars: ‘Kokur Belyi 46-10-3’, ‘Kokur Belyi 46-10-6’, ‘Solnechnodolinsky’, ‘Solnechnaya Dolina 40’, ‘Solnechnaya Dolina 65’, ‘Sykh Dane’, ‘Sary рandas’, ‘Muscat Krymskui’, ‘Mahrovatchik’, ‘Kokur Krasnyi’, ‘Bezymyannyi’ and ‘Tsimladar’.

Abstract Introduction: Hypomethylating agents (HMA), including AZA, used to treat cytopenias in MDS patients (pts), can exacerbate thrombocytopenia. Such pts are usually treated with repeated platelet transfusions and AZA dose adjustments. Relieving thrombocytopenia may reduce platelet transfusion requirements and allow optimal AZA dosing. Eltrombopag is an oral TPO receptor agonist approved for the treatment of pts with chronic ITP, hepatitis C virus-related thrombocytopenia, and recurrent severe aplastic anemia. SUPPORT was a randomized, double-blind, placebo-controlled trial investigating the platelet supportive care effects of eltrombopag versus placebo in pts with intermediate (int)-1, int-2 or high-risk MDS receiving AZA. Methods :Adult pts with no previous exposure to HMA, baseline (BL) platelets <75x109/L and int-1, int-2 or high-risk MDS by IPSS were enrolled. Pts were randomized 1:1 to eltrombopag/AZA or placebo/AZA. Pts received eltrombopag or placebo starting at 200 mg/day (100 mg/day for East Asians), adjusted by 100 mg increments (50 mg for East Asians) to a maximum 300 mg/day (150 mg/day in East Asians) - to ensure platelet counts remained sufficient to avoid platelet transfusions and bleeding events - for as long as pts received AZA (75 mg/m2 sc once daily for 7 days, every 28 days). Treatment could continue as long as benefit was derived or until disease progression, unacceptable toxicity or death. Primary endpoint was proportion of platelet-transfusion independent pts during AZA cycles 1-4. Key secondary endpoints included overall survival (OS) and disease progression. Adverse events (AEs) were recorded from the first dose of treatment until completion of the 4-week follow-up period following discontinuation of study treatment. Following a planned interim assessment, an independent data monitoring committee recommended stopping the study prematurely because outcomes crossed the pre-defined futility threshold and for safety reasons. Here we report the primary analyses from all randomized pts at the time of trial termination. Results:356 pts (median age 70 [range 24-89] years) received eltrombopag (n=179; n=64 int-1, n=77 int-2, n=38 high-risk) or placebo (n=177; n=61 int-1, n=83 int-2, n=33 high-risk). 29 (16%) eltrombopag and 37 (21%) placebo pts were platelet-transfusion dependent at BL. Median time on AZA plus eltrombopag or placebo was 83 (range 1-477) vs 149 (8-503) days. Most common reasons (≥10%) for treatment discontinuation on eltrombopag or placebo, respectively, were study termination (32 vs 44%), AZA discontinuation (30 vs 26%) and AEs (22 vs 14%). Median eltrombopag or placebo doses were 113 (range 60-148) vs 122 (81-147) mg/day in East Asians and 200 (65-293) vs 262 (107-316) mg/day in non-East Asians. At an interim analysis (n=147 evaluable pts), 13/79 (16%) eltrombopag and 27/68 (40%) placebo pts were platelet-transfusion independent [OR: 0.25, 95% CI: 0.11, 0.61; one-sided P=1.000], crossing the pre-defined futility boundary. At premature (primary and final analysis) study termination (n=356), 28/179 (16%) eltrombopag and 55/177 (31%) placebo pts were platelet-transfusion independent during the first 4 cycles of AZA (OR: 0.37, 95% CI: 0.21, 0.65; one-sided P=1.000). At study closure, 57 (32%) and 51 (29%) pts had died in the eltrombopag and placebo arms, respectively, with 33 (19%) and 29 (16%) deaths within 30 days after end of treatment; the main causes of death (≥10%) were disease under study (16 vs 12%) and sepsis (10 vs 7%). Disease progression (investigator-assessed) had occurred in 38 (21%) and 30 (17%) pts in the eltrombopag and placebo groups, respectively, at the time of study discontinuation. The most common AEs for eltrombopag are summarized (Table). Conclusions: In contrast to published reports on eltrombopag monotherapy inducing platelet transfusion independence in MDS pts, eltrombopag given concomitantly with AZA was inferior to placebo/AZA. There was no difference in overall deaths between the two groups. A complete assessment of disease progression, including AML progression at the time of study termination, is in progress. Pharmacodynamic antagonism between AZA and eltrombopag is proposed as one potential explanation for these results; further analyses and preclinical studies are ongoing to determine a possible mechanism of drug-drug interaction and the impact of drug sequencing on this potential association. Disclosures Dickinson: GlaxoSmithKline: Consultancy, Research Funding. Fenaux:Celgene, Janssen, Novartis, Astex, Teva: Research Funding; Celegene, Novartis, Teva: Honoraria. Mittleman:Celgene, Novartis, Janssen: Speakers Bureau; Novartis, Pfizer, Janssen, Roche: Consultancy. Portella:Novartis: Employment. Burgess:Novartis: Employment. Platzbecker:Celgene Corporation: Honoraria, Research Funding; TEVA Pharmaceutical Industries: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

477 Background: HCC is increasingly prevalent in older adults with rising incidence and an aging population worldwide. Retrospective studies show older patients with HCC may have an increased survival compared to younger patients. However, data is lacking regarding the genomic and biologic differences, that if identified, would potentially change how we treat this disease in younger vs. older patients. Hence, there is a need to better characterize the molecular landscape of the disease in an age-specific manner. We analyzed the association of age with genomic alterations and therapeutic response to sorafenib in a cohort of advanced HCC that had undergone comprehensive molecular profiling. Methods: 487 HCC samples (excluding variants) were analyzed using Next Generation Sequencing (592 gene panel, NextSeq), Whole Exome and Whole Transcriptome Sequencing (NovaSeq), and IHC at Caris Life Sciences (Phoenix, AZ). PD-L1 positivity was determined by IHC (SP-142 clone, cutoff ≥1, 1%). Tumor mutational burden (TMB) was a measure of total somatic mutations per Mb. Immune cell populations were determined by Microenvironment Cell Population (MCP) counter analysis of RNA expression data. Overall survival (OS) calculated from tissue collection to last contact and time on treatment (TOT) with sorafenib were extracted from insurance claims and calculated using Kaplan-Meier curves. Statistical analysis was done using Chi-square, Fisher Exact and Wilcoxon rank sum tests, with p values adjusted for multiple comparisons and q<0.05. Results: Differences in the molecular landscape of HCC stratified by patient age were assayed using a ternary classification based on 1 standard deviation from the mean age (mean age=65; <53: A1 (n=51), 53-77: A2 (n=361), >77: A3 (n=75)). With age, mutational frequencies in CTNNB1 (A1=13.04%, A2=33.43%, A3=38.24%) and TERT (A1=25%, A2=68.84%, A3=76.92%) increased, while ATM (A1=6.52%, A2=0.93%, A3=1.49%) decreased (p<0.05, q>0.05). There were fold increases in median TMB (A2/A1=1.33, A3/A1=1.33, p<0.01), LAG3 (A2/A1=1.75, A3/A1=1.93 p<0.01), CTLA4 (A2/A1=2.05, A3/A1=2.15, p<0.05) expression; median cell fractions of CD8+ T cells (A2/A1=1.37, A3/A1=1.50, p<0.05) & B cells (A3/A1=3.01 p<0.05) increased while cancer associated fibroblasts (A1/A2=0.62, A1/A3=0.69, p<0.01) decreased with age. PD-L1 was not statistically significant. While there was no change in OS, reduced TOT with sorafenib was observed in patients aged>65 (p=0.013). Conclusions: Increased alterations in oncogenic drivers and estimates of CD8+ T cells and B cells were observed in the elderly population with HCC. The enhanced presence of co-inhibitory molecules suggests potential immune evasion. While we observed reduced TOT with sorafenib, additional studies are needed to elucidate the impact of molecular alterations on outcomes with sorafenib and newer therapies (i.e. immunotherapy) in older adults.

Introduction Rib fractures in the ≥65-year-old population have been shown to strongly influence mortality and pneumonia rates. There is a growing body of evidence demonstrating improvements in the geriatric patient’s survival statistics and respiratory performances after surgical stabilization of rib fractures (SSRF). We have observed a strong survival and complication avoidance trend in geriatric patients who undergo SSRF. The purpose of our study was to evaluate the outcomes of geriatric patients with rib fractures treated with SSRF compared to those who only receive conservative therapies. Methods We performed a retrospective review of our trauma registry analyzing outcomes of patients ≥65 years with rib fractures. Patients admitted from 2015 to 2019 receiving SSRF (RP group) were compared to a nonoperative controls (NO group) admitted during the same time. Bilateral fractures were excluded. Independent variables analyzed = ISS, mortalities, hospital days, ICU days, pleural space complications, and readmissions. Follow-up was 60 days after discharge. Group comparison was performed using Kolmogorov-Smirnov, Shapiro-Wilk, and Mann-Whitney U tests. Results 257 patients were analyzed: 172 in the NO group with mean age of 75 (65-10) and 85 in the RP group with mean age of 74 (65-96). Mean ISS = 13 (1-38) for the NO group and 20 (9-59) for the RP group ( P < .001). Mean hospital days = 8 (1-39) and 15 (3-49) in NO and RP groups, respectively. Mean ICU days = 10 (1-32) and 8 (1-11) in NO and RP groups, respectively. Deaths, pneumonia, readmissions, and pleural effusions in the NO group were statistically significant ( P < .01). Analysis of complications revealed 4 RP patients (4.7%) with respiratory complications out to 60 days and 65 NO patients (37.8%) ( P < .001). Conclusions Surgical stabilization of rib fractures appears to be associated with a survival advantage and an avoidance of respiratory-related complications in the ≥65-year-old patient population.

Objectives: Since pre-existing expectations, that is, beliefs, in a treatment may modify outcomes, and acupuncture studies often fail to measure expectations, we wanted to investigate the use of acupuncture, interest, and belief in acupuncture effects among patients undergoing cancer therapy. Method: A cross-sectional design, where the participants answered a study-specific questionnaire with questions regarding their use of, interest and belief in acupuncture treatment. Results: A total of 457 patients with cancer (48% men, mean age 65 years) answered the questionnaire. Acupuncture was used by 4 (1%) patients during their cancer therapy, and 368 (83%) expressed an interest in receiving acupuncture. Of the 457 patients, 289 (63%) believed acupuncture to be effective for at least 1 of 17 requested symptoms, most commonly pain (56% of the patients) and muscle tension (40%). They believed acupuncture to be effective for a mean value 3 of the 17 requested symptoms. Women ( P < .001), and patients 41 to 65 years ( P < .001), expressed a stronger belief in acupuncture effects than others. Conclusions: Men and older patients expressed weaker beliefs in acupuncture effects than other patients, indicating the importance of collecting expectancy data in future randomized sham-controlled acupuncture studies to be able to treat expectancy as an effect-modifier. The high interest and beliefs in acupuncture effects found also indicate that acupuncture should be available for patients with cancer, for side effects where acupuncture has shown to be effective. In a clinical setting, older men might need more encouragement regarding positive expected outcomes of the acupuncture treatment than younger women.

AimWe validated patientpain drawing (PPD) in establishing the diagnosis of chronic anterior compartment syndrome (CACS) in patients with exercise-induced leg pain.MethodsThe study comprised 477 consecutive patients, all suspected of having CACS. The diagnosis was based on the patient’s history, a thorough clinical examination and measurements of intramuscular pressure (IMP) following an exercise test. Patients completed a PPD before their hospital visit. Two independent orthopaedic surgeons diagnosed the causes of leg pain based only on the PPD at least 1 year after admission. Based on the results of diagnostic tests, the patients were divided into three groups: CACS (n=79), CACS with comorbidity (n=89) and non-CACS (n=306).ResultsThe sensitivity of the PPD to identify CACS correctly was 67% (observer 1) and 75% (observer 2). The specificity was 65% and 54%, respectively. The interobserver agreement (n=477) was 80%, and the kappa value was 0.55. The interobserver agreement was 77%, and the kappa value was 0.48 among 168 CACS patients with or without comorbidity. The interobserver agreement was 85%, and the kappa value was 0.56 in 79 CACS, and CACS was correctly diagnosed in 79% (observer 1) and 82% (observer 2). The test–retest showed the same results for the two observers, with an intraobserver agreement of 84%, while the test–retest reliability coefficient was 0.7. Comorbidity was found in 53% of CACS patients.ConclusionPPD might be a valuable instrument in diagnosing the causes of exercise-induced leg pain. It is useful in identifying CACS with and without comorbidity.

18505 Background: Lung cancer is increasingly diagnosed in elderly patients and is the first cause of cancer death. Treatment of this subset represents a challenge to medical oncologists. Methods: We retrospectively reviewed clinical characteristics, co-morbidity (Charlson Index), toxicity and results of all patients ≥ 65 years (y) old, diagnosed of advanced NSCLC. We compared these results with younger patients’. Results: From January-95 to June-02, we treated 477 patients (pt), 176 ≥ 65 years, 301 < 65 y. Treatment: 177 pt, MIC (mitomycine + ifosfamide + cisplatin), 60 ≥ 65 y and 117 < 65 y; 156, CG (Cisplatin + Gemcitabine), 52 > 65 y and 104 < 65 y; 144, CP (Cisplatin + Paclitaxel), 64 ≥ 65 y and 120 < 65 y. Characteristics: median age 60 (31–78); 428 male, 49 female; ECOG 0/1/2/3: 83/312/71/5, Stage IIIA, IIIB and IV: 72/199/206, Histology: squamous carcinoma 215, adenocarcinoma 190, large cell 19, bronchioloalveolar 7, undifferentiated 45 pt. No significant differences between the two groups. Overall response rate: 39% (CR, 32.9%, PR, 6.1%), Stable disease 26.4% and Progressive disease, 26.4%. Patients ≥ 65 y: CR 5.7%, PR 45.5%, SD 23.3% and PD 18.2%. Patients < 65 y: CR 6.3% PR 25.6%, SD 28.2% and PD 31.2%. Predictive factors for response: ECOG and stage. Response rate was superior in patients ≥ 65 y and in patients ≥ 70 y. Overall survival: 38.29 weeks (w): < 65 y, 38.57 w; 65–70 y, 37.71 w and ≥ 70 y, 37 w. Multivariate analysis: ECOG, stage and sex were prognostic factors; age, histology, Charlson index and schedule treatment were not significant. Grade 3/4 episodes of toxicity: ≥ 65 y, 184/17, and < 65 y, 232/8. Treatment delays: ≥ 65 y, 115 and < 65 y, 100. Hospitalization due to toxicity: >≥ 65 y, 34 and < 65 y, 23. Treatment was stopped in 13 pt >≥ 65 y and in 7 pt < 65 y. Conclusions: Age is not a predictive factor for response to chemotherapy, neither a prognostic factor for survival. Charlson index does not seem to be useful for these patients. Although toxicity is superior, cisplatin-based schedules are safe and active. No significant financial relationships to disclose.

9060 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. We have conducted this open-label phase I study to assess the PK, PD and tolerability of BCD-017. Methods: 24 healthy male volunteers signed the informed consent and were sequentially assigned to receive 1, 3 or 9 mg of BCD-017 or 5 mcg/kg/day of filgrastim for 7 days, 6 volunteers per group. Outcome measures included absolute neutrophil count (ANC) and СD34+ cell count, PK parameters and adverse events (AEs). Results: BCD-017 induced a fast and significant increase of ANC. Median maximum ANC (ANCmax) for BCD-017 1, 3, 9 mg and filgrastim was 18.68 (10.62-21.02), 25.92 (15.43-28.07), 32.22 (18.22-45.79), and 28.21 (21-31.95) ×103 cells/mm3, respectively; median time to ANCmax was 24 (12-24); 48 (24-72); 72 (48-72); and 132,5 (12-169) h, respectively; median increase in СD34+ cells number 96 h post dose was 4.7 (1.2-6.5), 6.5 (1.7-12.3), 40.9 (24.5-102), and 17.8 (3.3-35.2) times, respectively. Filgrastim serum concentration was analyzed using ELISA. Median Cmax for BCD-017 3 and 9 mg and filgrastim was 45 (31-65), 446 (191-649), and 40 (20-54) ng/mL, respectively; median Tmax was 48 (24-72), 36 (24-48), and 8 (6-8) h respectively; median T1/2 was 65 (51-70), 46 (41-57), and 6.7 (6.2-7.6) h, respectively. BCD-017 was well tolerated. No dose-limiting AEs were observed. AEs included headache, back pain, myalgia, arthralgia, thrombocytopenia, hyperuricemia, alkaline phosphatase/LDH increased. All AEs were of grade 1-2. Compared to filgrastim, the best tolerability was observed in 3 mg group. Conclusions: BCD-017 is shown to be a potent stimulator of granulopoiesis. BCD-017 3 mg did not differ from filgrastim in terms of ANC increase and its safety was shown in healthy volunteers. Further phase II study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving cytotoxic chemotherapy is necessary.