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1.
Gynecol Oncol ; 156(2): 265-270, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911006

RESUMO

Multiple practice changing studies were presented at the 2019 ESMO Congress in Barcelona, Spain. The ovarian cancer studies presented at the Presidential session will likely refine and redefine the initial treatment of ovarian cancer. Other compelling trial data in ovarian, uterine and cervical cancer were also unveiled. The key oral abstracts from this meeting are summarized in this meeting report.


Assuntos
Neoplasias dos Genitais Femininos/terapia , Ensaios Clínicos Fase III como Assunto , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
Anticancer Res ; 39(12): 6595-6602, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810925

RESUMO

BACKGROUND/AIM: Non-invasive biomarker detection using DNA from cell-free circulating DNA (cfDNA) and circulating tumor cells (ctcDNA) are emerging as they can be used for early diagnosis, prognosis and therapeutic target selection for cancer. However, cfDNA and ctcDNA from the same patient have not yet been compared extensively on how different the genetic characteristics of the two are in terms of the overlap between them. MATERIALS AND METHODS: The performance of a customized NGS panel was used to compare the variants found in the 20 pairs of cfDNA and ctcDNA from gynecological cancer patients. RESULTS: A genetic variant analysis revealed that there were only nine common overlapping variants out of 63 between the cfDNA and ctcDNA pairs, while 31 and 22 were unique to cfDNA and ctcDNA, respectively. CONCLUSION: A combinatory analysis of both cfDNA and CTCs from cancer patients can improve the sensitivity of liquid biopsies. These results are expected to provide better genetic target information for guiding clinical strategies for cancer.


Assuntos
Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Variação Genética , Neoplasias dos Genitais Femininos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , DNA de Neoplasias/genética , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos
3.
Gynecol Oncol ; 155(2): 301-304, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31575390

RESUMO

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD. METHODS: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity. RESULTS: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy. CONCLUSIONS: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Neoplasias dos Genitais Femininos/tratamento farmacológico , Cardiopatias/induzido quimicamente , Doxorrubicina/efeitos adversos , Substituição de Medicamentos , Ecocardiografia/métodos , Feminino , Cardiopatias/fisiopatologia , Cardiopatias/prevenção & controle , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Polietilenoglicóis/efeitos adversos , Angiografia Cintilográfica/métodos , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos
4.
Int J Mol Sci ; 20(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547532

RESUMO

Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias dos Genitais Femininos , Proteínas de Neoplasias , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/imunologia , Humanos , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia
5.
Eur J Oncol Nurs ; 42: 82-89, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473465

RESUMO

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) can interfere with activities of daily living and can negatively affect symptoms. Thus, this study aimed to develop and implement an aroma self-foot reflexology regimen based on Cox's Interaction Model of Client Health Behaviour (IMCHB) as an intervention that can be self-performed at home and at any time. The effects of aroma self-foot reflexology on peripheral neuropathy, peripheral skin temperature, anxiety, and depression were examined in patients with gynaecologic cancer who were undergoing chemotherapy. METHODS: This randomized controlled trial included 32 experimental and 31 control patients with CIPN. Data were collected using self-reported questionnaires (CIPN assessment tool, HADS). In the experimental group, peripheral neuropathy, peripheral skin temperature, anxiety, and depression were measured before and after aroma self-foot reflexology therapy for 6 weeks. The control group was provided with identical aroma self-foot reflexology training 6 weeks later and underwent the intervention at that time. RESULTS: The intervention resulted in lower levels of symptoms of peripheral neuropathy, less interference with activities (p < .001), and higher peripheral skin temperature level (p < .001). Anxiety and depression decreased in the experimental group (p < .001). The ratio of borderline and definite cases of anxiety and depression did not differ between groups. CONCLUSIONS: An aroma self-foot reflexology intervention can reduce CIPN, anxiety, and depression in gynaecologic cancer patients. Further research is required to assess the effects of differences in the content of the intervention and the effects of various numbers of applications and durations of applications based on each individual patient's condition.


Assuntos
Ansiedade/terapia , Depressão/terapia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Manipulações Musculoesqueléticas/métodos , Doenças do Sistema Nervoso Periférico/terapia , Temperatura Cutânea , Atividades Cotidianas , Adulto , Idoso , Ansiedade/diagnóstico , Ansiedade/etiologia , Depressão/diagnóstico , Depressão/etiologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/psicologia , Humanos , Massagem , Pessoa de Meia-Idade , Odorantes , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/psicologia , Inquéritos e Questionários
6.
Anticancer Res ; 39(8): 4555-4560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366559

RESUMO

BACKGROUND/AIM: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy. PATIENTS AND METHODS: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated. RESULTS: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1. CONCLUSION: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved.


Assuntos
Anorexia/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Ingestão de Alimentos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Adulto , Idoso , Anorexia/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/patologia , Vômito/induzido quimicamente , Vômito/epidemiologia , Vômito/patologia
8.
Integr Cancer Ther ; 18: 1534735419846392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31046491

RESUMO

OBJECTIVE: The aim of this study was to assess the potential risks of interactions between biologically based complementary and alternative medication (BB-CAM) and conventional drugs during systemic therapy in breast and gynecological cancer patients by analyzing the actual CAM-drug combinations from individual patients' records. METHODS: From September 2014 to December 2014 and from February 2017 to May 2017, all patients (n = 717) undergoing systemic therapy at the Gynecologic Oncology Day Care Unit in the Gynecology and Obstetrics Department of the Technical University of Munich, Germany, were asked to participate in a questionnaire about all their medications. To assess the potential risk of CAM-drug interactions (CDIs), we initially utilized the Lexicomp drug interaction database. This assessment was then expanded with a systematic search of other digital databases, such as the National Center for Complementary and Integrative Health, Memorial Sloan Kettering Cancer Center, PubMed, and MEDLINE as well as the Cochrane Library. RESULTS: Among 448 respondents, 74.1% reported using BB-CAM simultaneously with their systemic therapy. The assessment showed 1 patient with a potentially clinically relevant CDI, where the interaction was based on a self-medicated combination of Echinacea and cyclophosphamide. Furthermore, 81 patients (18.1%) were thought to have interactions because of a combination of BB-CAMs and cytochrome P450 3A4-metabolized anticancer drugs. CONCLUSIONS: Our data demonstrated high overall use of BB-CAMs by cancer patients undergoing systemic therapy. The analyses showed only 1 clinically relevant CDI.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Interações Ervas-Drogas/fisiologia , Terapias Complementares/métodos , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
J Korean Acad Nurs ; 49(2): 149-160, 2019 Apr.
Artigo em Coreano | MEDLINE | ID: mdl-31064968

RESUMO

PURPOSE: The purpose of this study was to examine the effects of oral cryotherapy on oral mucositis, reactive oxygen series, inflammatory cytokines, and oral comfort in patients undergoing chemotherapy for gynecologic cancers. METHODS: Participants were randomly assigned to the experimental group (n=25, receiving oral cryotherapy during chemotherapy) and the control group (n=25, receiving the usual care consisting of 0.9% normal saline gargles three times before meals). Oral mucositis was assessed using the oral assessment guide, while oral comfort was assessed using the oral perception guide. Reactive oxygen series was measured as total oxidant stress, and the level of two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were examined. The data were analyzed using t-test, chi-square test, Fisher's exact test, Mann-Whitney U-test, and repeated measures analysis of variance. RESULTS: There was a significant difference in the oral mucositis score, reactive oxygen series score, TNF-α level, and oral comfort score between the two groups, and there were significant changes over time and in the group-by-time interactions. There was a significant difference in the IL-6 score between the two groups, but there were no significant changes over time or in the group-by-time interactions. CONCLUSION: The study results revealed that oral cryotherapy was more effective than the usual care regime of normal saline gargles for reducing oral mucositis, reactive oxygen series, and inflammatory cytokines and for improving oral comfort in gynecologic cancer patients undergoing chemotherapy.


Assuntos
Crioterapia , Interleucina-6/análise , Espécies Reativas de Oxigênio/metabolismo , Estomatite/terapia , Fator de Necrose Tumoral alfa/análise , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estresse Oxidativo , Estomatite/etiologia
10.
Am Soc Clin Oncol Educ Book ; 39: e152-e166, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099646

RESUMO

Epithelial ovarian cancer has a very high rate of relapse after primary therapy; historically approximately 70% of patients with a complete clinical response to surgery and adjuvant chemotherapy will relapse and die of the disease. Although this number has slowly improved, cure rates remain less than 50%. As such, maintenance therapy with the aim of preventing or delaying disease relapse and the goal of improving overall survival has been the subject of intense study. Numerous earlier studies with agents ranging from radioactive phosphorus to extended frontline therapy or to monthly taxol administration demonstrated encouraging improvements in progression-free survival (PFS) only to find, disappointingly, no benefit in overall survival. In addition, the PFS advantage of maintenance therapy was associated with disconcerting side effects such that maintenance therapy was not adapted as standard of care. Studies with bevacizumab and PARP inhibitors have demonstrated a PFS advantage with a manageable side-effect profile. However, an overall survival advantage remains unclear, and the use of these approaches thus remains controversial. Furthermore, in recurrent disease, the length of chemotherapy and benefits of extended chemotherapy is unclear. Thus, additional trials assessing maintenance strategies in ovarian and other gynecologic malignancies are needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Quimioterapia de Consolidação , Resistencia a Medicamentos Antineoplásicos , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/etiologia , Neoplasias dos Genitais Femininos/mortalidade , Humanos , Quimioterapia de Manutenção , Terapia de Alvo Molecular , Recidiva , Projetos de Pesquisa , Resultado do Tratamento
11.
Tumori ; 105(3): 253-258, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30945623

RESUMO

PURPOSE: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel. METHODS: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage. RESULTS: Fifty-two percent of patients in arm A (P=0.406), 59% in arm B (P=0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms. CONCLUSIONS: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.


Assuntos
Neoplasias dos Genitais Femininos/tratamento farmacológico , Náusea/tratamento farmacológico , Olanzapina/administração & dosagem , Vômito/tratamento farmacológico , Adulto , Idoso , Carboplatina/efeitos adversos , Dexametasona/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Humanos , Itália , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/patologia , Paclitaxel/efeitos adversos , Palonossetrom/efeitos adversos , Inquéritos e Questionários , Vômito/induzido quimicamente , Vômito/epidemiologia , Vômito/patologia
12.
Gynecol Oncol ; 153(3): 694-702, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30929824

RESUMO

Antibody drug conjugates (ADCs) are an exciting class of oncologic therapeutics. ADCs have been FDA approved in hematologic malignancies and breast cancer and are a growing area of study in numerous solid malignancies. The desire for tumor-specific therapies with decreased systemic toxicity has driven over a decade of research into the design and optimization of ADCs, which are now in a third generation of development. Gynecologic malignancies in particular suffer a dearth of novel therapies. This review will examine the field of ADCs in gynecologic cancers, focusing on ADCs targeting folate receptor alpha (FRα), mesothelin, tissue factor, MUC16 (CA125), NaPi2B, and Trop2.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Imunoconjugados/uso terapêutico , Maitansina/análogos & derivados , Antígenos de Neoplasias , Antígeno Ca-125 , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Moléculas de Adesão Celular/antagonistas & inibidores , Desenho de Fármacos , Feminino , Receptor 1 de Folato/antagonistas & inibidores , Proteínas Ligadas por GPI/antagonistas & inibidores , Humanos , Maitansina/uso terapêutico , Proteínas de Membrana/antagonistas & inibidores , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/antagonistas & inibidores , Tromboplastina/antagonistas & inibidores
13.
Gynecol Oncol ; 154(1): 199-206, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30987772

RESUMO

OBJECTIVE: Endocrine therapy is often considered as a treatment for hormone-responsive gynecologic malignancies. In breast cancer, activating mutations in the estrogen receptor (mutESR1) contribute to therapeutic resistance to endocrine therapy, especially aromatase inhibitors (AIs). The purpose of this study was to evaluate the frequency and clinical relevance of ESR1 genomic alterations in gynecologic malignancies. METHODS: DNA from FFPE tumor tissue obtained during routine clinical care for 9645 gynecologic malignancies (ovary, fallopian tube, uterus, cervix, vagina, vulvar, and placenta) was analyzed for all classes of genomic alterations (base substitutions (muts), insertions, deletions, rearrangements, and amplifications) in ESR1 by hybrid capture next generation sequencing. A subset of alterations was characterized in laboratory-based transcription assays for response to endocrine therapies. RESULTS: A total of 295 ESR1 genomic alterations were identified in 285 (3.0%) cases. mutESR1 were present in 86 (0.9%) cases and were more common in uterine compared to other cancers (2.0% vs <1%, respectively p < 0.001). mutESR1 were enriched in carcinomas with endometrioid versus serous histology (4.4% vs 0.2% respectively, p < 0.0001 in uterine and 3.5% vs 0.3% respectively, p = 0.0004 in ovarian carcinomas). In three of four patients with serial sampling, mutESR1 emerged under the selective pressure of AI therapy. Despite decreased potency of estrogen receptor (ER) antagonists in transcriptional assays, clinical benefit was observed following treatment with selective ER-targeted therapy, in one case lasting >48 months. CONCLUSIONS: While the prevalence of ESR1 mutations in gynecologic malignancies is low, there are significant clinical implications useful in guiding therapeutic approaches for these cancers.


Assuntos
Inibidores da Aromatase/administração & dosagem , Receptor alfa de Estrogênio/genética , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/genética , Moduladores Seletivos de Receptor Estrogênico/administração & dosagem , Adulto , Inibidores da Aromatase/farmacologia , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Transcrição Genética/efeitos dos fármacos , Transcriptoma , Resultado do Tratamento , Adulto Jovem
14.
Int J Med Mushrooms ; 21(3): 225-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002607

RESUMO

A review of scientific information about the potential role of medicinal mushrooms in the prevention and treatment of gynecological cancers, human immunodeficiency virus, and human papillomavirus infections is reported here. The results of in vivo and in vitro experiments on 16 different species of Basidiomycetes and three Ascomycetes, which possess chemopreventive potential and are effective in clinical application in combination with chemotherapy, are also discussed. Medicinal mushroom extracts confirm an evident efficacy on the reduction of tumor cell proliferation and side effects in patients with gynecological tumors who are undergoing chemotherapy treatments. This review, the first on the use of medicinal mushrooms in the prevention and treatment of gynecological cancers, aims to highlight the remarkable potential of mushrooms in integrated oncology.


Assuntos
Agaricales/química , Produtos Biológicos/uso terapêutico , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/prevenção & controle , Animais , Antioxidantes/uso terapêutico , Ascomicetos/química , Basidiomycota/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios Clínicos como Assunto , Feminino , HIV/efeitos dos fármacos , Humanos , Camundongos , Papillomaviridae/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias Vaginais/tratamento farmacológico , Neoplasias Vaginais/prevenção & controle
15.
BMC Cancer ; 19(1): 386, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023249

RESUMO

BACKGROUND: Previous neurocognitive assessments in non-central nervous system cancers highlight the high incidence of neurocognitive dysfunction in this study population. However, there have been few studies exploring neurocognitive dysfunction induced by chemotherapy in gynecological cancer patients. This prospective longitudinal study was conducted to assess neurocognitive functioning and functional brain networks in Chinese gynecological cancer patients pre- and post-chemotherapy, while additionally including age-matched healthy subjects as the control group. METHODS: All research participants were evaluated using a resting-state functional magnetic resonance imaging and neurocognition assessment. Behavioral data were conducted using SPSS for descriptive statistics, correlation and comparison analyses. Preprocessing of MRI (Magnetic Resonance Imaging) data and network analyses were performed using GRETNA (Graph Theoretical Network Analysis). RESULTS: A total of 40 subjects joined this study, with 20 subjects in each group. With the exception of the mean of psychomotor speed, there was no significant difference pre-chemotherapy between patients and healthy controls in neurocognitive test mean scores (Ps > 0.05). During the post-chemotherapy assessment, there were significant differences in the mean scores of neurocognitive tests (including Digit Span tests, verbal memory, immediate recall, delayed recall, and information processing speed tests) (all Ps < 0 .05). Longitudinal graph analysis revealed statistically significant differences in the patient group, with significant decreases in both local efficiency (P < 0.01) and global efficiency (P = 0.04). Lower raw TMT-A scores were significantly associated with lower local efficiency (r = 0.37, P = 0.03). Lower verbal memory scores were statistically significant and associated with lower global efficiency (r = 0.54, P = 0.02) in the patient group, but not in the healthy control group. CONCLUSIONS: This study found that the risk of brain function and neurocognitive changes following chemotherapy could potentially guide patients in making appropriate treatment decisions, and this study may identify a cohort that could be suited for study of an intervention.


Assuntos
Encéfalo/fisiopatologia , Disfunção Cognitiva/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Neoplasias dos Genitais Femininos/complicações , Transtornos Neurocognitivos/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Neoplasias dos Genitais Femininos/diagnóstico por imagem , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Transtornos Neurocognitivos/induzido quimicamente , Transtornos Neurocognitivos/diagnóstico por imagem , Testes Neuropsicológicos
16.
Semin Oncol Nurs ; 35(2): 217-219, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30876683

RESUMO

OBJECTIVE: To review recent therapies approved by the US Food and Drug Administration for the treatment of gynecologic malignancies. DATA SOURCES: PubMed, FDA.gov, ASCO.org. CONCLUSION: The landscape for treating gynecologic malignancies is rapidly changing. Maintenance therapy now exists for women with advanced ovarian cancer after completing chemotherapy for both newly diagnosed and platinum-sensitive recurrent ovarian cancer. Anti-angiogenic therapy has many applications in gynecologic malignancies. Immunotherapy can be used in certain situations for women with gynecologic malignancies. IMPLICATIONS FOR NURSING PRACTICE: Biologic agents and immunotherapy have distinct side-effect profiles that nurses need to be aware of to optimize patient care and outcomes.


Assuntos
Neoplasias dos Genitais Femininos/tratamento farmacológico , Antineoplásicos/uso terapêutico , Aprovação de Drogas , Feminino , Neoplasias dos Genitais Femininos/classificação , Humanos , Estados Unidos , United States Food and Drug Administration
17.
BMJ Open ; 9(1): e024357, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30782732

RESUMO

INTRODUCTION: Carboplatin (CBDCA) administered at a dosage of 4 mg/mL/min or more area under the blood concentration-time curve (AUC) is considered to be ranked as the highest chemotherapy-induced nausea and vomiting (CINV) risk of the moderately emetogenic chemotherapy agents. The complete response (CR) rate for preventing overall CINV, defined as no emetic episodes and no use of rescue medication, for standard triplet antiemetic therapy (5-HT3RA, 5-hydroxytryptamine-3 receptor antagonist; NK1RA, neurokinin-1 receptor antagonist; DEX, dexamethasone) was approximately 60% in gynaecological cancer patients receiving CBDCA-based therapy. Further improvement in antiemetic treatment is needed to optimise care. This trial is to evaluate the efficacy and safety of using 5 mg olanzapine (OLZ) plus standard triplet antiemetic therapy for CINV after AUC ≥4 mg/mL/min CBDCA combination therapy in gynaecological cancer patients. METHODS AND ANALYSIS: This trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1-4, after supper) in combination with 5-HT3RA, NK1RA and DEX. The primary endpoint is the CR rate during the overall period (0-120 hours). Testing the hypothesis that this regimen can improve CR rate from 60% (null hypothesis) to 75% (alternative hypothesis) with a one-sided type I error of 0.1 and power of 0.8 will require 53 patients. Considering the dropout rate, the target sample size is set at 60. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000031646.


Assuntos
Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Náusea/prevenção & controle , Antagonistas do Receptor de Neuroquinina-1/uso terapêutico , Olanzapina/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/prevenção & controle , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Carboplatina/efeitos adversos , Quimioterapia Combinada , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Granisetron/uso terapêutico , Humanos , Morfolinas/uso terapêutico , Náusea/induzido quimicamente , Resultado do Tratamento , Vômito/induzido quimicamente
18.
Gynecol Oncol ; 153(2): 304-311, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30792002

RESUMO

OBJECTIVES: Conducting clinical trials in rare malignancies is challenging due to the limited number of patients and differences in biologic behavior. We investigated the feasibility and clinical utility of using genomic profiling for rare gynecologic malignancies. METHODS: Rare epithelial gynecologic cancer patients were analyzed for somatic variants through an institutional molecular profiling program using the Sequenom MassArray platform or the TruSeq Amplicon Cancer Panel on the MiSeq platform. Clinical trial outcomes by RECIST 1.1, and time on treatment were evaluated. RESULTS: From March 2012 to November 2015, 767 gynecologic patients were enrolled and 194 (27%) were classified as rare epithelial malignancies. At least one somatic mutation was identified in 72% of patients, most commonly in TP53 (39%), KRAS (28%) and PIK3CA (27%). A total of 14% of patients were treated on genotype-matched trials. There were no significant differences in overall response rate between genotype-matched versus unmatched trials, nor in median time on treatment between genotype trials and the immediate prior systemic standard treatment. Among 13 evaluable Low Grade Serous ovarian cancer patients treated on genotype-matched trials with MEK inhibitor-based targeted combinations, there were four partial responses. CONCLUSIONS: Somatic molecular profiling is feasible and enables the identification of patients with rare gynecologic cancers who are candidates for genotype-matched clinical trials. Genotype-matched trials, predominantly MEK-based combinations in KRAS and/or NRAS mutant Low Grade Serous ovarian cancer patients, and genotype-unmatched trials, have shown potential clinical activity. Prospective trials with integrated genotyping are warranted to assess the clinical utility of next generation sequencing tests as a standard clinical application in rare malignancies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias dos Genitais Femininos/tratamento farmacológico , Técnicas de Genotipagem/estatística & dados numéricos , Doenças Raras/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Estudos de Viabilidade , Feminino , Neoplasias dos Genitais Femininos/genética , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Mutação , Seleção de Pacientes , Estudos Prospectivos , Doenças Raras/genética , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto Jovem
19.
Arch Pharm Res ; 42(2): 128-139, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30684192

RESUMO

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) induces conformational and functional changes to numerous key signaling molecules following proline-directed phosphorylation and its deregulation contributes to disease, particularly cancer. PIN1 is overexpressed in breast cancer, promoting cell proliferation and transformation in collaboration with several oncogenic signaling pathways, and is correlated with a poor clinical outcome. PIN1 level is also increased in certain gynecological cancers such as cervical, ovarian, and endometrial cancers. Although women with breast cancer are at risk of developing a second primary gynecological malignancy, particularly of the endometrium and ovary, the common oncogenic signaling pathway mediated by PIN1 has not been noted to date. This review discusses the roles of PIN1 in breast tumorigenesis and gynecological cancer progression, as well as the clinical effect of targeting this enzyme in breast and gynecological cancers.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Neoplasias dos Genitais Femininos/metabolismo , Peptidilprolil Isomerase de Interação com NIMA/metabolismo , Animais , Antineoplásicos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos/tendências , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Humanos , Peptidilprolil Isomerase de Interação com NIMA/antagonistas & inibidores , Ligação Proteica/fisiologia
20.
Gynecol Oncol ; 153(1): 158-164, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30630630

RESUMO

OBJECTIVE: Aberrant expression of HER2/neu and PIK3CA gene products secondary to amplification/mutations are common in high-grade-serous-endometrial (USC) and ovarian-cancers (HGSOC). Because scant information is currently available in the literature on the potential negative effect of PIK3CA mutations on the activity of afatinib, in this study we evaluate for the first time the role of oncogenic PIK3CA mutations as a potential mechanism of resistance to afatinib in HGSOC and USC overexpressing HER2/neu. METHODS: We used six whole-exome-sequenced primary HGSOC/USC cell-lines and three xenografts overexpressing HER2/neu and harboring mutated or wild-type PIK3CA/PIK3R1 genes to evaluate the role of PI3K-mutations as potential mechanism of resistance to afatinib, an FDA-approved pan-c-erb-inhibitor in clinical trials in USC. Primary-USC harboring wild-type-PIK3CA gene was transfected with plasmids encoding oncogenic PIK3CA-mutations (H1047R/E545K). The effect of afatinib on HER2/PI3K/AKT/mTOR pathway was evaluated by immunoblotting. RESULTS: We found PI3K wild-type cell-lines to be significantly more sensitive (lower IC50) than PI3K-mutated cell-lines p = 0.004). In vivo, xenografts of primary cell-line USC-ARK2, transfected with the PIK3CA-H1047R or E545K hotspot-mutations, exhibited significantly more rapid tumor growth when treated with afatinib, compared to mice harboring ARK2-tumors transfected with wild-type-PIK3CA (p = 0.041 and 0.001, respectively). By western-blot, afatinib effectively reduced total and phospho-HER2 proteins in all cell-lines. However, H1047R/E545K-PIK3CA-transfected-ARK2-cells demonstrated a greater compensatory increase in phosphorylated-AKT proteins after afatinib exposure when compared to controls ARK2. CONCLUSIONS: Oncogenic PI3K mutations may represent a major mechanism of resistance to afatinib. Combinations of c-erb with PIK3CA, AKT or mTOR inhibitors may be necessary to more efficiently block the PIK3CA/AKT/mTOR pathway.


Assuntos
Afatinib/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Neoplasias dos Genitais Femininos/tratamento farmacológico , Fosfatidilinositol 3-Quinases/genética , Adulto , Idoso , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases/biossíntese , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Neoplasias dos Genitais Femininos/enzimologia , Neoplasias dos Genitais Femininos/genética , Humanos , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Mutação , Fosfatidilinositol 3-Quinases/biossíntese , Inibidores de Proteínas Quinases/farmacologia , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
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