Diagnóstico y tratamiento quirúrgico de una paciente con una neoplasia trofoblástica gestacional / Diagnosis and surgical treatment of a patient with gestational trophoblastic neoplasia

Resumen ANTECEDENTE: La neoplasia trofoblástica gestacional forma parte del grupo de afecciones derivadas de la proliferación anómala del trofoblasto con capacidad para invasión y metástasis. CASO CLÍNICO: Paciente de 42 años, asintomática, con sospecha ecográfica de mola hidatiforme. El legrado uterino y el estudio anatomopatológico confirmaron el diagnóstico de mola hidatiforme completa. Con la cuantificación consecutiva de tres elevaciones de la β-HCG se diagnosticó: neoplasia trofoblástica gestacional. Se estadificó en estadio I, bajo riesgo y ante el deseo genésico satisfecho la paciente aceptó la histerectomía más salpingectomía bilateral. En el seguimiento posterior la paciente se encontró asintomática, con determinaciones seriadas de b-HCG negativa y ecografías vaginales sin hallazgos. CONCLUSIÓN: La histerectomía con salpingectomía bilateral puede ser el tratamiento definitivo en casos seleccionados de neoplasia trofoblástica. La evidencia disponible es escasa, por lo que es necesario seguir investigando en este campo.

Abstract BACKGROUND: Gestational trophoblastic neoplasia is one of a group of conditions resulting from abnormal trophoblast proliferation with capacity for invasion and metastasis. CLINICAL CASE: 42-year-old asymptomatic patient with ultrasound suspicion of hydatidiform mole. Uterine curettage and anatomopathological study confirmed the diagnosis of complete hydatidiform mole. With the consecutive quantification of three elevations of β-HCG a diagnosis of gestational trophoblastic neoplasia was made. It was staged as stage I, low-risk, and the patient agreed to hysterectomy plus bilateral salpingectomy. At subsequent follow-up the patient was found to be asymptomatic, with negative serial determinations of β-HCG and vaginal ultrasound scans without findings. CONCLUSION: Hysterectomy with bilateral salpingectomy may be the definitive treatment in selected cases of trophoblastic neoplasia. The available evidence is scarce and further research is needed in this field.

Avapritinib Versus Regorafenib in Locally Advanced Unresectable or Metastatic GI Stromal Tumor: A Randomized, Open-Label Phase III Study.

PURPOSE: Primary or secondary mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) underlie tyrosine kinase inhibitor resistance in most GI stromal tumors (GISTs). Avapritinib selectively and potently inhibits KIT- and PDGFRA-mutant kinases. In the phase I NAVIGATOR study (NCT02508532), avapritinib showed clinical activity against PDGFRA D842V-mutant and later-line KIT-mutant GIST. VOYAGER (NCT03465722), a phase III study, evaluated efficacy and safety of avapritinib versus regorafenib as third-line or later treatment in patients with unresectable or metastatic GIST. PATIENTS AND METHODS: VOYAGER randomly assigned patients 1:1 to avapritinib 300 mg once daily (4 weeks continuously) or regorafenib 160 mg once daily (3 weeks on and 1 week off). Primary end point was progression-free survival (PFS) by central radiology per RECIST version 1.1 modified for GIST. Secondary end points included objective response rate, overall survival, safety, disease control rate, and duration of response. Regorafenib to avapritinib crossover was permitted upon centrally confirmed disease progression. RESULTS: Four hundred seventy-six patients were randomly assigned (avapritinib, n = 240; regorafenib, n = 236). Median PFS was not statistically different between avapritinib and regorafenib (hazard ratio, 1.25; 95% CI, 0.99 to 1.57; 4.2 v 5.6 months; P = .055). Overall survival data were immature at cutoff. Objective response rates were 17.1% and 7.2%, with durations of responses of 7.6 and 9.4 months for avapritinib and regorafenib; disease control rates were 41.7% (95% CI, 35.4 to 48.2) and 46.2% (95% CI, 39.7 to 52.8). Treatment-related adverse events (any grade, grade ≥ 3) were similar for avapritinib (92.5% and 55.2%) and regorafenib (96.2% and 57.7%). CONCLUSION: Primary end point was not met. There was no significant difference in median PFS between avapritinib and regorafenib in patients with molecularly unselected, late-line GIST.

Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial.

BACKGROUND: PDGFRA D842V mutations occur in 5-10% of gastrointestinal stromal tumours (GISTs), and previously approved tyrosine kinase inhibitors (TKIs) are inactive against this mutation. Consequently, patients have a poor prognosis. We present an updated analysis of avapritinib efficacy and long-term safety in this patient population. METHODS: NAVIGATOR (NCT02508532), a two-part, open-label, dose-escalation/dose-expansion phase I study, enrolled adult patients with unresectable GISTs. Patients with PDGFRA D842V-mutant GIST were a prespecified subgroup within the overall safety population, which included patients who received ≥1 avapritinib dose. Primary end-points were overall response rate (ORR) and avapritinib safety profile. Secondary end-points were clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS). Overall survival (OS) was an exploratory end-point. RESULTS: Between 7 October 2015 and 9 March 2020, 250 patients enrolled in the safety population; 56 patients were included in the PDGFRA D842V population, 11 were TKI-naïve. At data cut-off, median follow-up was 27.5 months. Safety profile was comparable between the overall safety and PDGFRA D842V populations. In the PDGFRA D842V population, the most frequent adverse events were nausea (38 [68%] patients) and diarrhoea (37 [66%]), and cognitive effects occurred in 32 (57%) patients. The ORR was 91% (51/56 patients). The CBR was 98% (55/56 patients). The median DOR was 27.6 months (95% confidence interval [CI]: 17.6-not reached [NR]); median PFS was 34.0 months (95% CI: 22.9-NR). Median OS was not reached. CONCLUSION: Targeting PDGFRA D842V-mutant GIST with avapritinib resulted in an unprecedented, durable clinical benefit, with a manageable safety profile. Avapritinib should be considered as first-line therapy for these patients.

Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy.

BACKGROUND: Most gastrointestinal stromal tumors (GIST) driven by KIT or platelet-derived growth factor receptor A (PDGFRA) mutations develop resistance to available tyrosine kinase inhibitor (TKI) treatments. NAVIGATOR is a two-part, single-arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST. MATERIALS AND METHODS: Eligible patients were 18 years or older with histologically or cytologically confirmed unresectable GIST and Eastern Cooperative Oncology Group performance status ≤2 and initiated avapritinib at 300 mg or 400 mg once daily. Primary endpoints were safety in patients who initiated avapritinib at 300 mg or 400 mg once daily and overall response rate (ORR) in patients in the safety population with three or more previous lines of TKI therapy. RESULTS: As of November 16, 2018, in the safety population (n = 204), the most common adverse events (AEs) were nausea (131 [64%]), fatigue (113 [55%]), anemia (102 [50%]), cognitive effects (84 [41%]), and periorbital edema (83 [41%]); 17 (8%) patients discontinued due to treatment-related AEs, most frequently confusion, encephalopathy, and fatigue. ORR in response-evaluable patients with GIST harboring KIT or non-D842V PDGFRA mutations and with at least three prior therapies (n = 103) was 17% (95% confidence interval [CI], 10-25). Median duration of response was 10.2 months (95% CI, 7.2-10.2), and median progression-free survival was 3.7 months (95% CI, 2.8-4.6). CONCLUSION: Avapritinib has manageable toxicity with meaningful clinical activity as fourth-line or later treatment in some patients with GIST with KIT or PDGFRA mutations. IMPLICATIONS FOR PRACTICE: In the NAVIGATOR trial, avapritinib, an inhibitor of KIT and platelet-derived growth factor receptor A tyrosine kinases, provided durable responses in a proportion of patients with advanced gastrointestinal stromal tumors (GIST) who had received three or more prior therapies. Avapritinib had a tolerable safety profile, with cognitive adverse events manageable with dose interruptions and modification in most cases. These findings indicate that avapritinib can elicit durable treatment responses in some patients with heavily pretreated GIST, for whom limited treatment options exist.

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors.

BACKGROUND: Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18-mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence-based guidance on management of avapritinib-associated adverse events (AEs), including cognitive effects and intracranial bleeding. MATERIALS AND METHODS: We performed a post hoc analysis of data from a two-part, single-arm dose escalation/expansion phase I study (NAVIGATOR; NCT02508532) in patients with U/M GISTs treated with oral avapritinib 30-600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression-free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose). RESULTS: Of 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18-mutation; 66.8% started avapritinib at 300 mg. The most common treatment-related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment-related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all-cause cognitive effects rate (grade 1-2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3-3.1 weeks) than without (4.9-7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without. CONCLUSION: Tolerability-guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs. IMPLICATIONS FOR PRACTICE: Early recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment-related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events.

Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial.

BACKGROUND: Targeting of KIT and PDGFRA with imatinib revolutionised treatment in gastrointestinal stromal tumour; however, PDGFRA Asp842Val (D842V)-mutated gastrointestinal stromal tumour is highly resistant to tyrosine kinase inhibitors. We aimed to assess the safety, tolerability, and antitumour activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal stromal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NAVIGATOR). METHODS: NAVIGATOR is a two-part, open-label, dose-escalation and dose-expansion, phase 1 study done at 17 sites across nine countries (Belgium, France, Germany, Poland, Netherlands, South Korea, Spain, the UK, and the USA). Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 2 or less, and with adequate end-organ function were eligible to participate. The dose-escalation part of the study included patients with unresectable gastrointestinal stromal tumours. The dose-expansion part of the study included patients with an unresectable PDGFRA D842V-mutant gastrointestinal stromal tumour regardless of previous therapy or gastrointestinal stromal tumour with other mutations that either progressed on imatinib and one or more tyrosine kinase inhibitor, or only received imatinib previously. On the basis of enrolment trends, ongoing review of study data, and evolving knowledge regarding the gastrointestinal stromal tumour treatment paradigm, it was decided by the sponsor's medical director together with the investigators that patients with PDGFRA D842V mutations would be analysed separately; the results from this group of patients is reported in this Article. Oral avapritinib was administered once daily in the dose-escalation part (starting dose of 30 mg, with increasing dose levels once daily in continuous 28-day cycles until the maximum tolerated dose or recommended phase 2 dose was determined; in the dose-expansion part, the starting dose was the maximum tolerated dose from the dose-escalation part). Primary endpoints were maximum tolerated dose, recommended phase 2 dose, and safety in the dose-escalation part, and overall response and safety in the dose-expansion part. Safety was assessed in all patients from the dose-escalation part and all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour in the dose-expansion part, and activity was assessed in all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour who received avapritinib and who had at least one target lesion and at least one post-baseline disease assessment by central radiology. This study is registered with ClinicalTrials.gov, NCT02508532. FINDINGS: Between Oct 26, 2015, and Nov 16, 2018 (data cutoff), 46 patients were enrolled in the dose-escalation part, including 20 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour, and 36 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour were enrolled in the dose-expansion part. At data cutoff (Nov 16, 2018), 38 (46%) of 82 patients in the safety population (median follow-up of 19·1 months [IQR 9·2-25·5]) and 37 (66%) of the 56 patients in the PDGFRA D842V population (median follow-up of 15·9 months [IQR 9·2-24·9]) remained on treatment. The maximum tolerated dose was 400 mg, and the recommended phase 2 dose was 300 mg. In the safety population (patients with PDGFRA D842V-mutant gastrointestinal stromal tumour from the dose-escalation and dose-expansion parts, all doses), treatment-related grade 3-4 events occurred in 47 (57%) of 82 patients, the most common being anaemia (14 [17%]); there were no treatment-related deaths. In the PDGFRA D842V-mutant population, 49 (88%; 95% CI 76-95) of 56 patients had an overall response, with five (9%) complete responses and 44 (79%) partial responses. No dose-limiting toxicities were observed at doses of 30-400 mg per day. At 600 mg, two patients had dose-limiting toxicities (grade 2 hypertension, dermatitis acneiform, and memory impairment in patient 1, and grade 2 hyperbilirubinaemia in patient 2). INTERPRETATION: Avapritinib has a manageable safety profile and has preliminary antitumour activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumours. FUNDING: Blueprint Medicines.

Selective Killing of SMARCA2- and SMARCA4-deficient Small Cell Carcinoma of the Ovary, Hypercalcemic Type Cells by Inhibition of EZH2: In Vitro and In Vivo Preclinical Models.

The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition. It has been recently reported that ovarian cancers with dual loss of the redundant SWI/SNF components SMARCA4 and SMARCA2 are characteristic of a rare rhabdoid-like subtype known as small-cell carcinoma of the ovary hypercalcemic type (SCCOHT). Here, we provide evidence that a subset of commonly used ovarian carcinoma cell lines were misdiagnosed and instead were derived from a SCCOHT tumor. We also demonstrate that tazemetostat, a potent and selective EZH2 inhibitor currently in phase II clinical trials, induces potent antiproliferative and antitumor effects in SCCOHT cell lines and xenografts deficient in both SMARCA2 and SMARCA4. These results exemplify an additional class of rhabdoid-like tumors that are dependent on EZH2 activity for survival. Mol Cancer Ther; 16(5); 850-60. ©2017 AACR.

Use and influence of Delivery and Birth Plans in the humanizing delivery process / Uso e influência dos Planos de Parto e Nascimento no processo de parto humanizado / Uso e influencia de los Planes de Parto y Nacimiento en el proceso de parto humanizado

get to know, analyze and describe the current situation of the Delivery and Birth Plans in our context, comparing the delivery and birth process between women who presented a Delivery and Birth Plan and those who did not.

conhecer, analisar e descrever a situação atual dos Planos de Parto e Nascimento no contexto estudado, comparando o processo de parto e sua finalização entre as mulheres que apresentaram e as que não apresentaram um Plano de Parto e Nascimento.

conocer, analizar y describir la situación actual de los Planes de Parto y Nacimiento en nuestro entorno, comparando el proceso de parto y la finalización del mismo entre las mujeres que han presentado un Plan de Parto y Nacimiento y las que no lo han hecho.

Seguridad del paciente y competencia enfermera en el almacenamiento y conservación de los botiquines de las unidades de hospitalización de un hospital universitario / Patients safety and nursing competences regarding drug storage in hospital units at a University Hospital

Resumen:

La seguridad del paciente es un tema actual e importante y son muchas las campañas, planes y estrategias en estudios e investigaciones de diversos países, dirigidas a minimizar los errores de medicación. Objetivo: evaluar el correcto almacenamiento y conservación de la medicación termolábil, fotosensible y la identificación de los medicamentos de alto riesgo. Material y método: estudio cuantitativo y transversal. Se evaluaron todos los botiquines en abril de 2013. Resultados: de las 16 unidades estudiadas, 14 (87,5%) mostraron algunos medicamentos fotosensibles incorrectamente protegidos de la luz. Igualmente, 14 unidades (87,5%) no tenían la totalidad de sus medicamentos de alto riesgo identificados como tal. Respecto a los termolábiles el 100% presentó un correcto almacenamiento y conservación.

Conclusiones: el correcto almacenamiento y conservación de los medicamentos es vital para garantizar su calidad, eficacia y seguridad, por lo que resulta imprescindible su conocimiento por parte de los y las enfermeras dada su competencia en la administración de los mismos.

Abstract:

Patients safety is a contemporary and significant issue, with many campaigns, plans and strategies aimed at minimizing drug mistakes being now investigated in several countries. Purpose: To asses correct storage for heat-sensitive, photosensitive drugs and to identify drugs at a high risk. Material and methods: A quantitative cross-sectional study. All medicine cabinets were evaluated in April 2013. Results: Among 16 hospital units, 14 (87.5%) had some photosensitive drugs inadequately protected from light. Furthermore, 14 units (87.5%) did not store all such medicines adequately identified as high-risk drugs. Regarding heat-sensitive drugs, all of them were correctly stored. Conclusions: Appropriate drug storage is essential to ensure drug quality, efficacy and safety. Thus, adequate understanding by nursing staff is needed because nurses are responsible for drug administration.

A segurança do paciente é um tema atual e importante e são muitas as campanhas, os planos e as estratégias em estudos e pesquisas de diversos países, destinadas a minimizar os erros de medicação. Objetivo: avaliar o adequado armazenamento e conservação de medicamentos termolábeis, fotossensíveis e a identificação dos que são de alto risco. Material e Método: estudo quantitativo e transversal. Foram avaliados todos os kits de medicamentos em abril de 2013. Resultados: das 16 unidades estudadas, 14 (87,5%) apresentaram alguns medicamentos fotossensíveis indevidamente protegidos da luz. Da mesma forma, 14 unidades (87,5%), não tinham todos os seus medicamentos de alto risco identificados como tal. Quanto aos termolábeis, 100% apresentaram um armazenamento e uma conservação adequada. Conclusões: o armazenamento e a conservação adequada dos medicamentos é vital para garantir a sua qualidade, eficácia e segurança, por isso, é essencial o conhecimento de enfermagem devido à sua competência na administração dos mesmo.

Job satisfaction among health care workers: the role of gender and age / Influência do gênero e da idade: satisfação no trabalho de profissionais da saúde / Influencia del género y edad: satisfacción laboral de profesionales sanitarios

OBJECTIVE: to analyze the influence of gender and age on the quality of the professional lives of health care professionals at a university hospital. METHOD: a total of 546 professionals completed a general questionnaire that measured sociodemographic variables and evaluated job satisfaction using a scale adopted from the NTP 394 Job Satisfaction scale and translated into Spanish. RESULTS: overall, 77.2% of the professionals surveyed were satisfied with the work they perform. With regards to gender, we found overwhelming evidence of the feminization of practically all health care professions included in the study, with higher levels of job satisfaction among women than men. Regarding age, 20-30-year-olds and professionals over 61 years old showed higher satisfaction levels than did middle-aged professionals. Higher levels of dissatisfaction were reported by professionals between 41 and 50 years old. CONCLUSIONS: we were able to detect the influence of gender and age on the level of job satisfaction, finding significant associations between job satisfaction and both of these variables. Generally, women expressed more satisfaction than men, and elderly professionals showed higher satisfaction compared to younger professionals. Management policies should focus on taking action to correct the conditions that produce dissatisfaction among certain groups of employees. .

OBJETIVO: analisar a influência do gênero e da idade na satisfação no trabalho de profissionais da saúde num hospital universitário. MÉTODO: a amostra foi constituída por 546 profissionais, aos quais foi administrado um questionário genérico, contendo variáveis sociodemográficas e um questionário específico, o NTP 394: Satisfação no Trabalho: Escala de Satisfação Global adaptada e validada para o castelhano. RESULTADOS: de modo geral, 77,2% da amostra manifestou estar satisfeita com o trabalho que realiza. Quanto ao gênero, foi evidenciada a feminização de praticamente todas as profissões em saúde, sem exceções, sendo que as mulheres manifestaram níveis mais elevados de satisfação. Com relação à idade, as faixas etárias que manifestaram os níveis mais elevados de satisfação foram entre 20 e 30 anos e acima de 61 anos. Em contrapartida, os profissionais entre 41 e 50 anos de idade apresentaram níveis de insatisfação. CONCLUSÕES: pode-se estabelecer a influência do gênero e da idade nos níveis de satisfação no trabalho da amostra estudada, visto que foram identificadas associações significativas. Em relação ao gênero, as mulheres manifestaram estar mais satisfeitas e, com respeito à idade, os maiores níveis de satisfação foram manifestos pelos participantes mais idosos. Sendo assim, as políticas de gestão devem focar na implantação de ações destinadas a melhorar as variáveis que se associam à insatisfação. .

OBJETIVO: analizar la influencia del género y edad en la satisfacción de la vida laboral en los profesionales sanitarios de un Hospital Universitario. MÉTODO: la muestra quedó constituida por 546 profesionales, administrándose un cuestionario general con variables sociodemográficas y otro específico, el NTP 394 Satisfacción Laboral: escala general de satisfacción adaptada y validada al castellano. RESULTADOS: en general un 77,2% se encuentra satisfecho con el trabajo que desempeña. En relación al género, se evidencia la feminización de prácticamente todas las profesiones sanitarias sin excepción, quedando patente niveles de satisfacción superior en las mujeres. La edad, presenta niveles más elevados de satisfacción en profesionales de edades entre 20 y 30 años y en los mayores de 61; en contrapartida los niveles de insatisfacción se presentan en los profesionales de edades comprendidas entre 41 y 50 años. CONCLUSIONES: podemos delimitar la influencia del género y la edad en los niveles de satisfacción laboral, obteniéndose asociaciones significativas en ambas variables; respecto al género, las mujeres se muestran más satisfechas y en cuanto a la edad los profesionales de mayor edad muestran mayor satisfacción. Así, las líneas de gestión deben orientarse al establecimiento de acciones de mejora en aquellas variables que producen insatisfacción. .

A phase II trial of Sunitinib malate in recurrent and refractory ovarian, fallopian tube and peritoneal carcinoma.

OBJECTIVE: Ovarian cancer is a highly angiogenic tumor and a model for antiangiogenic research. The tyrosine kinase receptor inhibitors target several receptors allowing for the pharmacological disruption of several independent pathways. Sunitinib malate is a multitargeted tyrosine kinase inhibitor. A phase II study utilizing a modified dosing schedule was conducted to assess the efficacy and safety of Sunitinib in recurrent ovarian, fallopian tube and peritoneal carcinoma. METHODS: A nonrandomized phase II study was modeled as a two-stage Simon design initially enrolling 17 evaluable participants in stage one and 18 patients in stage two. Patients received the study drug at 37.5mg every day over a 28 day treatment cycle until clinical or radiological evidence of progressive disease. Disease was evaluated radiographically and best overall response was defined using the RECIST 1.0 criteria. The primary objective of this study was to define the response rate (defined as complete response and partial response) while the secondary objectives included both the progression free rate as well as the safety of this agent in this patient population. RESULTS: The response rate (PR+CR) was 8.3% (95% confidence interval: 1.8%, 22.5%). The 16-week and 24 week progression-free survival estimate was 36% (95% confidence interval and 19.2%), respectively. The median progression-free survival estimate was 9.9 weeks. Hypertension and gastrointestional events were the most common toxicities noted. CONCLUSIONS: A modest response rate of 8.3% was achieved with Sunitinib malate. This phase II study adds to the body of literature of VEGFR inhibitors and further underscores the need of defining a genetic angiogenic signature.

Albuminuria as a marker of kidney and cardio-cerebral vascular damage. Isle of Youth Study (ISYS), Cuba.

INTRODUCTION: The disease complex comprised of atherosclerosis, chronic kidney disease (CKD) and other associated chronic vascular diseases is the leading cause of mortality worldwide. Microalbuminuria is a marker for vascular damage in the heart, kidney and brain. This paper presents selected findings of the clinical-epidemiological Isle of Youth Study (ISYS) of markers for kidney and vascular damage from chronic vascular diseases and their common risk factors in total population, focusing on Phase 2 reassessment (in 2010) of Phase 1 (2004 to 2006) results. OBJECTIVES: (1) Update the prevalence of risk factors in the study population aged ≥20 years (adult population). (2) Confirm presence of microalbuminuria in at-risk adults diagnosed as presumptive positives in Phase I. (3) Evaluate association between microalbuminuria and selected risk factors. METHODS: Of 3779 adults positive for microalbuminuria in ISYS Phase 1, 73.1% were reevaluated. The risk-factor questionnaire was re-administered and blood pressure, weight and height were measured. Blood was tested for creatinine, glycemia, cholesterol and triglycerides. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Albuminuria was measured in urine using Micral-Test (Germany) and albumin/creatinine ratio (ACR) by nephelometry. This paper uses ACR as the reference for analyzing risk factor associations. Double-entry tables were developed to analyze association among microalbuminuria, risk factors and co-morbidities. RESULTS: Most prevalent risks were hypertension, consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), excess weight and hypertriglyceridemia. Microalbuminuria was confirmed in 18% of cases, using the same test. Elevated prevalence of microalbuminuria was positively associated with advancing age, male sex, underweight, smoking, NSAID use, dyslipidemia, hypertension, diabetes, heart disease and stroke. CONCLUSIONS: The at-risk cohort studied presented low levels of confirmation for positive microalbuminuria. Positive microalbuminuria stratified individuals at greatest risk, except for obesity.

Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors.

PURPOSE New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. PATIENTS AND METHODS An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage > or = IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m(2) IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. CONCLUSION The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

Phase II trial of GM-CSF in women with asymptomatic recurrent müllerian tumors.

OBJECTIVE: GM-CSF is a recombinant human cytokine, which promotes the proliferation and differentiation of granulocytes and monocytes, and is associated with anti-tumor activity. The primary objective was to define the median time to treatment termination (TTT) with women with relapsed ovarian cancer treated with single agent GM-CSF delivered subcutaneously (SC). PATIENTS AND METHODS: Open label phase II study in asymptomatic patients with recurrent müllerian malignancy without an indication for immediate systemic chemotherapy. In the first cohort of 35 women, GM-CSF 250 microg/m(2) was administered SC on days 1-14 of a 28-day cycle, the second cohort received continuous GM-CSF 150 microg/m(2) given with dose escalation. RESULTS: Seventy-two women were enrolled. Best overall response included one complete response, and 20 patients with stable disease (23%), 4 of whom had stable disease for >6 months. Median TTT was 78 days. Toxicity in both cohorts was generally mild; however, four patients experienced excessive toxicity and withdrew consent. In the first cohort, CA-125 dropped in 70% of women from their baseline on study value (median change -23%, range -48 to +116%) after 14 days of GM-CSF. The magnitude of CA-125 drop during the first 2 weeks of therapy also showed a positive inverse correlation with day 15 white cell count for the whole group (p=0.038). CONCLUSION: GM-CSF is well tolerated and frequently associated with a decline in CA-125 that is correlated with leukocytosis. Although median TTT is modest, a subset of women had prolonged stable disease.

Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.

PURPOSE: Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit. PATIENTS AND METHODS: We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months. CONCLUSION: Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.

Phase II study of carboplatin and pemetrexed for the treatment of platinum-sensitive recurrent ovarian cancer.

PURPOSE: More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent epithelial ovarian cancer (EOC). Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combined with carboplatin to treat other cancers. PATIENTS AND METHODS: This is a phase II study of carboplatin area under the curve 5 with pemetrexed 500 mg/m(2) administered intravenously on day 1 every 21 days for six cycles or for up to eight cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors; other end points included toxicities, progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-five patients were accrued; 44 patients received treatment. Overall response rate was 51.1%; there were no complete responses (0%), 23 confirmed partial responses (51.1%), two unconfirmed partial responses (4.4%), 14 patients with stable disease (31.1%), and two patients with progressive disease after two cycles (4.4%). Grade 3 and 4 hematologic toxicities included neutropenia (41%), thrombocytopenia (23%), and anemia (9%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxicities included fatigue (11%), nausea (5%), vomiting (5%), diarrhea (5%), syncope (5%), and pulmonary embolism (5%). Median PFS time was 7.57 months (95% CI, 6.44 to 10.18 months), mean OS time was 20.3 months, and median OS has not yet been reached with a mean follow-up time of 15.3 months. CONCLUSION: Carboplatin/pemetrexed is a well-tolerated regimen with activity in platinum-sensitive recurrent EOC; further testing of this regimen in platinum-sensitive EOC patients is warranted.

Screening for domestic violence in an oncology clinic: barriers and potential solutions.

PURPOSE/OBJECTIVES: To evaluate the implementation of a domestic violence screening protocol in an oncology clinic. DESIGN: A retrospective review of a random sample of clinic medical records and qualitative surveys of nursing staff. SETTING: A gynecologic oncology clinic in a large teaching hospital. SAMPLE: 204 charts were abstracted and six oncology nurses completed surveys. METHODS: A random sample of patients from clinic appointment schedules was selected 6 and 12 months after the implementation of a domestic violence screening protocol. A brief written survey of nursing staff also was conducted. MAIN RESEARCH VARIABLES: Documentation of domestic violence screening, barriers to screening and documentation, and potential solutions to the barriers. FINDINGS: Sixty-three percent of the charts reviewed had a domestic violence screening record present, but only 12% of the charts with a screening record had documentation. Patients with domestic violence screening documentation were more likely to have had five or more clinic visits during the study period. The most frequent barriers to protocol implementation cited by nursing staff were forgetting to screen or document domestic violence screening. Nursing staff recommended adding domestic violence screening questions to forms and providing reminders to screen. CONCLUSIONS: Several barriers to successful implementation of a domestic violence screening protocol in a gynecologic oncology clinic, including documentation issues, were encountered. IMPLICATIONS FOR NURSING: Nurses interested in implementing a domestic violence screening protocol in their oncology clinic should consider reviewing the barriers to domestic violence screening and documentation and the potential solutions identified in this study.

Demographic, risk factor, and knowledge differences between Latinas and non-Latinas referred to colposcopy.

OBJECTIVE: Disparities occur in the incidence and mortality of cervical cancer among minority women in the US. Screening lowers cervical cancer incidence. Screening rates are lower for minority women than for White women in the US. This study sought to identify demographic, risk factor, and perception of the role of Pap smears between Latinas and non-Latinas. METHODS: A written survey was administered to 150 Latinas and 150 non-Latinas attending a colposcopy unit. Data on demographics, risk factors, screening rates, knowledge about cervical cancer screening, and perceived barriers to participation in screening programs were collected. RESULTS: A total of 140 Latinas and 146 non-Latinas completed the survey. Marital status and health insurance status were similar in the two groups. 30% of Latinas and 73.3% of non-Latinas reported completing college (p<0.0001). Only 55.7% of Latinas were employed, compared to 82.2% of non-Latinas (p<0.0001). 21% of Latinas and 53.4% of non-Latinas reported an annual income greater than 35,000 dollars (p<0.0001). Among Latinas, women with 1-5 lifetime Pap smears were less likely to have completed college than those with more than 5 lifetime Pap smears (OR=2.11; 95% CI 1.05-4.22) and to have an annual income of less than 35,000 dollars (OR=3.81; 95% CI 1.64-8.87). Latinas were less likely to have > or =6 lifetime sexual partners, use tobacco, and have a history of sexually transmitted infections. Latinas more commonly reported fear of test results (OR, 0.04; 95% CI 0.02-0.09) and inability to communicate with their provider in Spanish (p<0.0001) as barriers to screening than the non-Latina respondents. CONCLUSIONS: Several of the barriers limiting access to cervical cancer screening programs are also present among screened Latinas undergoing further evaluation for abnormal Pap smears.