RESUMEN
BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care. METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process. CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Humanos , Laparotomía , Atención Perioperativa/métodos , Organizaciones , Procedimientos Quirúrgicos ElectivosRESUMEN
BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Humanos , Cuidados Posoperatorios , Laparotomía , Atención Perioperativa/métodos , Procedimientos Quirúrgicos Electivos/métodosRESUMEN
A key function of clinical ethics services (CESs) is to provide decision-making support to health care providers in ethically challenging cases. Cases referred for ethics consultation are likely to involve diverging views or conflict, or to confront the boundaries of appropriate medical practice. Such cases might also attract legal action due to their contentious nature. As CESs become more prevalent in Australia, this article considers the potential legal liability of a CES and its members. With no reported litigation against a CES in Australia, we look to international experience and first principles. We consider the prospects of a claim in negligence, the most likely legal action against a CES, through application of legal principles to a hypothetical case scenario. We conclude that, although unlikely to be successful at this time, a CES could face answerable claims in negligence brought by patients (and families) who are the subject of ethics case consultation.
Asunto(s)
Ética Clínica , Mala Praxis , Humanos , Responsabilidad Legal , AustraliaRESUMEN
There is an increasing demand for the return of raw genomic data by research participants in translational genomic research. This article discusses the scope and application of privacy and freedom of information legislative provisions in Australia. Whether there is a right to access a copy of such data under Australian privacy legislation is contingent on whether raw genomic data can identify an individual and this article explores the opportunities for genomic data to be linked to individuals. We conclude that despite the complexity and overlapping nature of privacy laws in Australia, there is a clear right on the part of research participants to access their raw genomic data.
Asunto(s)
Confidencialidad , Privacidad , Humanos , Australia , GenómicaRESUMEN
AIMS: To evaluate the effect of an intimate partner violence intervention education component on nurses' attitudes in addressing intimate partner violence; complementary aims included understanding nurses' perceptions of the education and how it influenced their attitudes and confidence to address intimate partner violence in practice. DESIGN: An explanatory sequential mixed methods design embedded within a 15-site cluster randomized clinical trial that evaluated an intimate partner violence intervention within the Nurse-Family Partnership programme. METHODS: Data were collected between February 2011 and September 2016. Quantitative assessment of nurses' attitudes about addressing intimate partner violence was completed by nurses in the intervention (n = 77) and control groups (n = 101) at baseline, 12 months and at study closure using the Public Health Nurses' Responses to Women Who Are Abused Scale. Qualitative data were collected from nurses in the intervention group at two timepoints (n = 14 focus groups) and focused on their perceptions of the education component. Data were analysed using content analysis. RESULTS: Nurses in the intervention group reported large improvements in their thoughts, feelings and perceived behaviours related to addressing intimate partner violence; a strong effect of the education was found from baseline to 12 months and baseline to study closure timepoints. Nurses reported that the education component was acceptable and increased their confidence to address intimate partner violence. CONCLUSION: Nurses reported improved attitudes about and confidence in addressing intimate partner violence after receiving the education component. However, these findings need to be considered together with trial results showing no main effects for clients, and a low level of intervention fidelity. IMPACT: These evaluation findings underscore that improvement in nurses' self-reported educational outcomes about addressing intimate partner violence cannot be assumed to result in adherence to intervention implementation or improvement in client outcomes. These are important considerations for developing nurse education on intimate partner violence.
Asunto(s)
Violencia de Pareja , Enfermeras y Enfermeros , Actitud , Femenino , Grupos Focales , HumanosRESUMEN
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.
Asunto(s)
Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Manejo de la Enfermedad , Femenino , Humanos , Terapia Neoadyuvante , Resultado del TratamientoRESUMEN
Importance: Intimate partner violence (IPV) is a public health problem with significant adverse consequences for women and children. Past evaluations of a nurse home visitation program for pregnant women and first-time mothers experiencing social and economic disadvantage have not consistently shown reductions in IPV. Objective: To determine the effect on maternal quality of life of a nurse home visitation program augmented by an IPV intervention, compared with the nurse home visitation program alone. Design, Setting, and Participants: Cluster-based, single-blind, randomized clinical trial at 15 sites in 8 US states (May 2011-May 2015) enrolling 492 socially disadvantaged pregnant women (≥16 years) participating in a 2.5-year nurse home visitation program. Interventions: In augmented program sites (n = 229 participants across 7 sites), nurses received intensive IPV education and delivered an IPV intervention that included a clinical pathway to guide assessment and tailor care focused on safety planning, violence awareness, self-efficacy, and referral to social supports. The standard program (n = 263 participants across 8 sites) included limited questions about violence exposure and information for abused women but no standardized IPV training for nurses. Main Outcomes and Measures: The primary outcome was quality of life (WHOQOL-BREF; range, 0-400; higher score indicates better quality of life) obtained through interviews at baseline and every 6 months until 24 months after delivery. From 17 prespecified secondary outcomes, 7 secondary end points are reported, including scores on the Composite Abuse Scale, SPAN (Startle, Physiological Arousal, Anger, and Numbness), Prime-MD Patient Health Questionnaire, TWEAK (Tolerance/Worry About Drinking/Eye-Opener/Amnesia/C[K]ut Down on Drinking), Drug Abuse Severity Test, and the 12-Item Short-Form Health Survey (physical and mental health), version 2. Results: Among 492 participants enrolled (mean age, 20.4 years), 421 (86%) completed the trial. Quality of life improved from baseline to 24 months in both groups (change in WHOQOL-BREF scores from 299.5 [SD, 54.4] to 308.2 [SD, 52.6] in the augmented program group vs from 293.6 [SD, 56.4] to 316.4 [SD, 57.5] in the standard program group). Based on multilevel growth curve analysis, there was no statistically significant difference between groups (modeled score difference, -4.9 [95% CI, -16.5 to 6.7]). There were no statistically significant differences between study groups in any of the secondary participant end points. There were no adverse events recorded in either group. Conclusions and Relevance: Among pregnant women experiencing social and economic disadvantage and preparing to parent for the first time, augmentation of a nurse home visitation program with a comprehensive IPV intervention, compared with the home visitation program alone, did not significantly improve quality of life at 24 months after delivery. These findings do not support the use of this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT01372098.
Asunto(s)
Visita Domiciliaria , Violencia de Pareja/prevención & control , Mujeres Embarazadas , Calidad de Vida , Adolescente , Adulto , Mujeres Maltratadas , Femenino , Número de Embarazos , Humanos , Enfermeros de Salud Comunitaria , Embarazo , Método Simple Ciego , Adulto JovenRESUMEN
Disclosure of genetic information without consent of the patient (proband) challenges the legal frameworks of privacy and confidentiality. Changes to privacy legislation enable and provide guidelines for undertaking disclosure, with the purpose of reducing the harm to genetic relatives who, armed with such information, may seek predictive testing themselves. Nevertheless, significant uncertainty remains for health care professionals in the application of the discretion to disclose genetic information to at-risk relatives. First, jurisdictional inconsistencies in privacy legislation present challenges for the provision of genetic services across the country. Second, the current guidelines provide insufficient clarity regarding the justification for disclosure of genetic information to reduce psychological harm to relatives. Third, the implications of a potential expansion of a legal duty of care to inform genetic relatives in some circumstances indicates that such a duty would be unduly burdensome for health care professionals, and suggests that revision of the threshold for use - rather than disclosure - of depersonalised genetic information may represent a pragmatic way forward.
Asunto(s)
Revelación , Privacidad Genética , Australia , Confidencialidad , Pruebas Genéticas , Humanos , Consentimiento InformadoRESUMEN
OBJECTIVE: Preclinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents. The objective of this prospective multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian, tubal or peritoneal cancer through the frequency of objective tumor responses (ORR). METHODS: Patients with measurable disease, acceptable organ function, performance statusâ¯≤â¯2, and one prior platinum containing regimen were eligible. A two-stage design was utilized with a target sample size of 22 and 30 subjects, respectively. Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately (20%) and served as a historical control for direct comparison. The present study was designed to determine if the regimen had an ORR of ≥40% with 90% power. RESULTS: Fifty-eight patients were enrolled, of whom 2 received no study treatment and were inevaluable. The median number of cycles was 3 (268 total cycles, range 1-18). The number of patients responding was 11 (19.6%; 90% CI 11.4% to 30.4%) with one complete response. The median progression-free survival and overall survival was 3.6â¯months and 13.3â¯months, respectively. The median ORR duration was 9.2â¯months. Percentages of subjects with grade 3 toxicity included: Neutropenia 9%; anemia 5%; metabolic 5%; nausea 4%; infection 4%; neurologic (mostly neuropathy) 4%; and vascular (mostly thromboembolism) 4%. There were no grade 4 toxicities reported. CONCLUSIONS: This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ClinicalTrials.gov Identifier: NCT00888615].
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Hidrazinas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de las Trompas Uterinas/patología , Femenino , Humanos , Hidrazinas/farmacología , Persona de Mediana Edad , Neoplasias Ováricas/patología , Paclitaxel/farmacología , Neoplasias Peritoneales/patologíaRESUMEN
One challenge for the legal provision of voluntary assisted dying is to ensure that the person requesting it is not coerced and has made the decision voluntarily. In the State of Victoria, Australia, s 8 of the Voluntary Assisted Dying Act 2017 (Vic) provides that a health practitioner is prevented from initiating a discussion about voluntary assisted dying in the course of providing health services to a person. The aim of the provision was to avoid coercion or undue influence by a health practitioner. In this article we address the meaning and application of s 8 and consider whether in practice this provision might have the effect of excluding access for individuals who may have been interested in voluntary assisted dying but were never aware that this was an option for them.
Asunto(s)
Legislación Médica , Suicidio Asistido/legislación & jurisprudencia , Humanos , VictoriaRESUMEN
OBJECTIVE: Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS: A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS: Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS: Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.
Asunto(s)
Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/patología , Melanoma/genética , Melanoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Femenino , GTP Fosfohidrolasas/genética , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas c-kit/genética , Estudios Retrospectivos , Adulto Joven , beta Catenina/genéticaAsunto(s)
Atención a la Salud , Personal de Salud , Genómica , Humanos , Obligaciones Morales , Derechos del PacienteRESUMEN
Wye Valley NHS Trust v Mr B [2015] EWCOP 60 illustrates the extent to which the wishes, feelings, beliefs, and values strongly expressed by a person who lacks decision-making capacity are to be considered in determining his best interests. Whilst not going as far as a supported decision-making model, as endorsed by the UN Convention on the Rights of Persons with Disabilities, the case exemplifies the participative ethos of the Mental Capacity Act 2005 and the requirement that the person lacking capacity should participate as fully as possible in any decision affecting him.
Asunto(s)
Atención a la Salud/legislación & jurisprudencia , Derechos Humanos/legislación & jurisprudencia , Competencia Mental/legislación & jurisprudencia , Participación del Paciente/legislación & jurisprudencia , Esquizofrenia Paranoide , Anciano , Humanos , Masculino , Medicina Estatal , Reino UnidoRESUMEN
Borderline ovarian tumors (BOTs) are less common than epithelial ovarian cancers (EOCs). Low-grade EOCs (LG-EOCs) occur even less frequently than BOTs. After primary therapy, recurrence rates of BOTs and LG-EOCs are significantly lower and the stage-adjusted survival is higher than for high-grade EOCs. Thus, determining the best management in terms of traditional ovarian cancer staging and debulking procedures is more challenging and has been recently brought to question. This article reviews the particulars of BOTs and LG-EOCs, their similarities and differences, and how they are best managed and treated, and emphasizes the major role of surgery and the controversial role of chemotherapy. Because these tumors disproportionately affect younger women, this review addresses ovarian preservation in circumstances when fertility or hormonal preservation is desired.
Asunto(s)
Neoplasias Ováricas/terapia , Femenino , Humanos , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patologíaRESUMEN
OBJECTIVE: To determine the adherence to hematologic chemotherapy hold parameters for the carboplatin and dose-dense paclitaxel chemotherapy regimen in patients with ovarian, fallopian tube, or primary peritoneal cancers. METHODS: This is a quality assessment survey study. All 26 NCCN Member Institutions were contacted electronically. Hematologic chemotherapy hold parameter values (absolute neutrophil count [ANC] and platelet count) on days 1, 8, and 15 of each cycle were queried. These hold parameters were compared with published data supporting the use of dose-dense chemotherapy regimens in ovarian cancer. RESULTS: The overall survey response rate was 85% (22/26 sites). Of responders, 27% (6 sites) were fully adherent with all hematologic hold parameters and 64% (14 sites) used hold parameters that differed from the published protocol. Specifically, all of these sites use hold parameters higher than those recommended in the literature. Two centers did not have center-specific hold parameters. CONCLUSIONS: Carboplatin and dose-dense paclitaxel chemotherapy has been shown to increase progression-free survival and overall survival in patients with stage II-IV ovarian, fallopian tube, or primary peritoneal cancers. However, our study found that two-thirds of queried sites had hold parameters higher than those in the published protocol. Using more stringent hold parameters may lead to compromised clinical outcomes. Further research is necessary to determine the optimal strategy to increase individual site adherence to chemotherapy hematologic hold parameters as specified in published trials.
Asunto(s)
Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/uso terapéutico , Femenino , Humanos , Neoplasias Ováricas/patología , Encuestas y CuestionariosRESUMEN
This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.
Asunto(s)
Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Femenino , HumanosAsunto(s)
Confidencialidad/legislación & jurisprudencia , Sistemas de Registros Médicos Computarizados/legislación & jurisprudencia , Relaciones Médico-Paciente , Derivación y Consulta/legislación & jurisprudencia , Australia , Humanos , Almacenamiento y Recuperación de la Información/legislación & jurisprudencia , Consentimiento Informado/legislación & jurisprudenciaRESUMEN
OBJECTIVES: To identify common barriers to teaching and training and to identify strategies that would be useful in developing future training programs in gynecologic oncology in low- and middle- income countries. METHODS: There is a lack of overall strategy to meet the needs of education and training in gynecologic oncology in low- and middle- income countries, the leaderships of sister societies and global health volunteers met at the European Society of Gynecologic Oncology in October 23, 2015. The challenges of the training programs supported by gynecologic oncology societies, major universities and individual efforts were presented and discussed. Strategies to improve education and training were identified. RESULTS: Major challenges include language barriers, limited surgical equipment, inadequate internet access, lack of local support for sustainability in training programs, inadequate pathology and radiation oncology, finance and a global deficiency in identifying sites and personnel in partnering or developing training programs. The leaderships identified various key components including consultation with the local Ministry of Health, local educational institutions; inclusion of the program into existing local programs, a needs assessment, and the development of curriculum and regional centers of excellence. CONCLUSIONS: Proper preparation of training sites and trainers, the development of global curriculum, the establishment of centers of excellence, and the ability to measure outcomes are important to improve education and training in gynecologic oncology in low- and middle- income countries.
Asunto(s)
Ginecología/educación , Oncología Médica/educación , Países en Desarrollo , Femenino , Salud Global , Ginecología/economía , Humanos , Oncología Médica/economía , Factores SocioeconómicosRESUMEN
Background: Laboratory blood testing incurs financial costs and the blood draws can increase discomfort, yet minimal data exists regarding routine testing in gynecologic oncology surgical patients. Additionally, an increasing number of gynecologic oncology surgeries are performed via a laparoscopic approach. Thus, further investigation into perioperative laboratory testing for gynecologic oncology patients is warranted. An increasing number of gynecologic oncology surgeries are performed via a laparoscopic approach. Thus, further investigation into perioperative laboratory testing for gynecologic oncology patients is warranted. Objective: The aims of this study were (1) to evaluate the frequency and etiology of perioperative laboratory test abnormalities in patients undergoing laparoscopic and laparotomy surgery in a gynecologic oncology service, and (2) to establish an evidence-based algorithm to reduce unnecessary laboratory testing. Materials and Methods: A single-institution retrospective study was completed, investigating laparoscopic and laparotomic surgeries over 4 years. Information on preoperative and postoperative laboratory data, surgical parameters, perioperative interventions, and patient demographics was collected. Quality-assurance data were reviewed. Data were tabulated and analyzed using Statistical Product and Service Solutions (SPSS) version 22. A Student's t-test was used to test for group differences for continuous variables with equal variance, the Mann-Whitney-U test for continuous variables when unequal variance was detected, and Pearson's χ2 was used to investigate categorical variables of interest. p-Values <0.05 were considered to be statistically significant. Logistic regression was performed to investigate the relationships among multiple predictors and each identified outcome. Results: The study included 481 subjects (168 laparoscopies, 313 laparotomies). Patients undergoing laparoscopy were, on average, younger (53.5 versus 57.4), with lower body mass indexes (29.7 versus 33.0) and lower rates of diabetes (10.7% versus 19.5%), compared to patients undergoing laparotomy. Overall, >98% of patients underwent at least one preoperative and postoperative laboratory test, totaling 8060 preoperative and 5784 postoperative results. The laparoscopy group was significantly less likely to have postoperative metabolic abnormalities or to undergo perioperative blood transfusion. Patients taking an angiotensin-converting-enzyme inhibitor, angiotensin-II-receptor blocker, or diuretic were significantly more likely to have elevated creatinine preoperatively (odds ratio [OR]: 5.0; p < 0.001) and postoperatively (OR: 7.1; p < 0.001), and this remained true for each group when divided by surgical approach. Perioperative complications meeting institutional quality assurance criteria occurred in 1.7% of laparoscopy patients compared to 11.8% of laparotomy patients (p < 0.001); perioperative laboratory testing was not a factor in the diagnosis of these complications. Conclusions: Clinically significant laboratory abnormalities are uncommon and are less likely to be found on routine perioperative testing in gynecologic oncology patients undergoing laparoscopy, compared to patients undergoing laparotomy. This suggests a role for limiting perioperative laboratory blood testing. (J GYNECOL SURG 32:111).
RESUMEN
BACKGROUND: Activation of the mitogen activated protein kinase pathway plays a pivotal role in cell proliferation and is frequently activated in endometrial cancer. We sought to evaluate the efficacy/safety of selumetinib, a selective MEK-1/2 inhibitor in women with recurrent endometrial cancer. METHODS: This was a phase II, single-arm, open-label study evaluating response and 6-month event-free survival (EFS) as primary endpoints. Eligible patients had measurable disease, 1-2 prior cytotoxic regimens, and performance status 0-2. Selumetinib 75mg PO BID was administered daily until progression or intolerance. One cycle was 28days. RESULTS: Fifty-four patients were enrolled; 2 were excluded due to improper pre-study treatment (1) and never treated (1), leaving 52 evaluable for efficacy/safety. Median age was 62; histology included endometrioid (58%), serous (17%) and mixed (23%). Seventeen patients (33%) had 2 prior cytotoxic regimens. The median number of cycles administered was 2 (1-34). Three (6%) patients had objective response (1 CR, 2 PR); 13 had SD as best response. The proportion of patients with 6-month EFS was 12%. Median EFS, progression-free and overall survival was 2.1, 2.3, and 8.5months, respectively. Drug-attributed grade 3/4 adverse events were observed (≥5%) were fatigue (15%), anemia (10%), pain (10%), extremity edema (8%), and dyspnea (6%). There was 1 grade 4 infection (renal), 1 grade 4 anemia, and 1 death due to hemorrhage (rectum). CONCLUSIONS: Selumetinib was tolerable in this population but did not meet pre-trial specifications for clinical efficacy.