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1.
Cureus ; 13(6): e16070, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34367741

RESUMO

Introduction Ovarian cancer is the fifth-leading cause of cancer-related mortality in US women. There are survival disparities between non-Hispanic black (NHB) and non-Hispanic white (NHW) women. We assessed if insurance status or extent of disease modified the effect of race/ethnicity on survival for ovarian cancer. Methods A historical cohort was assembled using the 2007-2015 National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) dataset. Adult NHB and NHW (>18 years) diagnosed with regional and distant ovarian cancer were included. The outcome was five-year cause-specific mortality. Multivariable Cox regression models were fitted, including race by the extent of disease and race by insurance status interaction terms. Results For each significant interaction, separate Cox models were fitted. In total 8,043 women were included. The insurance status/race interaction was not statistically significant, but the extent of disease modified the effect of race on survival. NHB survival was lower in regional disease (adjusted hazard ratio (HR) =1.6; 95% confidence interval (CI) 1.1-2.4), while there was no difference in survival between women with distant disease (adjusted HR =1.0; 95%CI 0.9-1.2). Conclusions Ovarian cancer mortality is similar between NHB and NHW women with the distant disease but higher in NHB women with regional disease. Further research should clarify whether this difference is due to access to quality cancer treatment or other factors affecting treatment response.

2.
J Clin Oncol ; 39(18): 2037-2048, 2021 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-33939491

RESUMO

PURPOSE: To provide recommendations for appropriate dosing of systemic antineoplastic agents in obese adults with cancer. METHODS: A systematic review of the literature collected evidence regarding dosing of chemotherapy, immunotherapy, and targeted therapies in obese adults with cancer. PubMed and the Cochrane Library were searched for randomized controlled trials, meta-analyses, or cohort studies published from November 1, 2010, through March 27, 2020. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: Sixty studies, primarily retrospective, were included in the review. Overall, the evidence supported previous findings that obese adult patients tolerate full, body-size-based dosing of chemotherapy as well as nonobese patients. Fewer studies have addressed the dosing of targeted therapies and immunotherapies in relation to safety and efficacy in obese patients. RECOMMENDATIONS: The Panel continues to recommend that full, weight-based cytotoxic chemotherapy doses be used to treat obese adults with cancer. New to this version of the guideline, the Panel also recommends that full, approved doses of immunotherapy and targeted therapies be offered to obese adults with cancer. In the event of toxicity, the consensus of the Panel is that dose modifications of systemic antineoplastic therapies should be handled similarly for obese and nonobese patients. Important areas for future research include the impact of sarcopenia and other measures of body composition on optimal antineoplastic dosing, and more customized dosing based on pharmacokinetic or pharmacogenetic factors.Additional information is available at www.asco.org/supportive-care-guidelines.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Obesidade/complicações , Antineoplásicos/efeitos adversos , Humanos , Revisões Sistemáticas como Assunto
3.
Obstet Gynecol ; 137(3): 423-429, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33543899

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), uses two primary receptors, type II transmembrane serine protease and angiotensin-converting enzyme-2, for priming and cellular invasion, respectively. Both proteins have been demonstrated to be present in different concentrations in females and males, which may explain a mechanism for the reported higher case-fatality rate in males. Despite the known sex difference in COVID-19 disease mortality, preliminary data suggest there are certain female populations, including pregnant and menopausal women and possibly polycystic ovarian syndrome patients who are more susceptible to COVID-19-related morbidity. This commentary analyzes the interplay between sex differences, hormones, and the immune function in each of these populations with respect to the risk and severity of COVID-19 and proposes biological rationales to explain these differences.


Assuntos
COVID-19/epidemiologia , COVID-19/genética , Predisposição Genética para Doença , Enzima de Conversão de Angiotensina 2/genética , Cromossomos Humanos X , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Menopausa/fisiologia , Morbidade , Síndrome do Ovário Policístico/epidemiologia , Gravidez , SARS-CoV-2/fisiologia , Serina Endopeptidases/genética , Fatores Sexuais
4.
Acad Med ; 95(9S A Snapshot of Medical Student Education in the United States and Canada: Reports From 145 Schools): S103-S106, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33626657
5.
J Clin Oncol ; 37(33): 3152-3165, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31479306

RESUMO

PURPOSE: To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS: An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS: A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor-positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS: In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
CA Cancer J Clin ; 68(4): 284-296, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29809280

RESUMO

In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and tumorigenesis to facilitate strategies for prevention and early detection. CA Cancer J Clin 2018;68:284-296. © 2018 American Cancer Society.


Assuntos
Carcinoma/epidemiologia , Neoplasias Ovarianas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , American Cancer Society , Carcinoma/diagnóstico , Detecção Precoce de Câncer , Feminino , Disparidades nos Níveis de Saúde , Humanos , Incidência , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Prognóstico , Estados Unidos/epidemiologia
7.
CA Cancer J Clin ; 66(1): 43-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26641959

RESUMO

Answer questions and earn CME/CNE The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.


Assuntos
Neoplasias da Mama/terapia , Sobreviventes , Adulto , Idoso , American Cancer Society , Imagem Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Detecção Precoce de Câncer , Feminino , Aconselhamento Genético , Humanos , Anamnese , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Exame Físico , Qualidade de Vida , Medição de Risco , Sobreviventes/psicologia , Estados Unidos , Adulto Jovem
8.
J Clin Oncol ; 34(6): 611-35, 2016 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-26644543

RESUMO

The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base. Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation. Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made.This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for Clinicians and Journal of Clinical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Cancer Society or the American Society of Clinical Oncology.


Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Promoção da Saúde , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Vigilância da População , Atenção Primária à Saúde/métodos , Sobreviventes , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Imagem Corporal/psicologia , Neoplasias da Mama/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Transtornos Cognitivos/etiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Fadiga/etiologia , Fadiga/terapia , Feminino , Aconselhamento Genético , Fogachos/tratamento farmacológico , Fogachos/etiologia , Humanos , Estilo de Vida , Linfedema/etiologia , Linfedema/terapia , Adesão à Medicação , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Manejo da Dor , Planejamento de Assistência ao Paciente , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/terapia
9.
J Clin Oncol ; 30(13): 1553-61, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22473167

RESUMO

PURPOSE: To provide recommendations for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. METHODS: The American Society of Clinical Oncology convened a Panel of experts in medical and gynecologic oncology, clinical pharmacology, pharmacokinetics and pharmacogenetics, and biostatistics and a patient representative. MEDLINE searches identified studies published in English between 1996 and 2010, and a systematic review of the literature was conducted. A majority of studies involved breast, ovarian, colon, and lung cancers. This guideline does not address dosing for novel targeted agents. RESULTS: Practice pattern studies demonstrate that up to 40% of obese patients receive limited chemotherapy doses that are not based on actual body weight. Concerns about toxicity or overdosing in obese patients with cancer, based on the use of actual body weight, are unfounded. RECOMMENDATIONS: The Panel recommends that full weight-based cytotoxic chemotherapy doses be used to treat obese patients with cancer, particularly when the goal of treatment is cure. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight-based doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese who are administered full weight-based doses. Clinicians should respond to all treatment-related toxicities in obese patients in the same ways they do for non-obese patients. The use of fixed-dose chemotherapy is rarely justified, but the Panel does recommend fixed dosing for a few select agents. The Panel recommends further research into the role of pharmacokinetics and pharmacogenetics to guide appropriate dosing of obese patients with cancer.


Assuntos
Antineoplásicos/administração & dosagem , Cálculos da Dosagem de Medicamento , Neoplasias/tratamento farmacológico , Obesidade/complicações , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Superfície Corporal , Peso Corporal , Medicina Baseada em Evidências , Humanos , Neoplasias/complicações , Farmacogenética , Padrões de Prática Médica , Resultado do Tratamento
10.
Clin Obstet Gynecol ; 54(4): 602-18, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22031250

RESUMO

One in 1000 pregnancies is complicated with cancer with the most common tumors being breast cancer, cervical cancer, thyroid, leukemia, lymphoma, and ovarian cancer. It is often assumed that cancer during pregnancy necessitates sacrificing the well-being of the fetus but in most cases appropriate treatment can be offered to the mother without placing the fetus at serious risk. The care of a pregnant woman with cancer involves evaluation of competing maternal and fetal risks and benefits. Although it is rare to administer chemotherapy during pregnancy, the risks depend on the drugs used and the gestational age of the fetus. During the period of organogenesis (4 to 13 wk), administration of cytotoxic drugs carries an increased risk of fetal malformations and fetal loss. Chemotherapy in the second or third trimester is associated with intrauterine growth retardation, prematurity, and low birth weight and bone marrow toxicity in many exposed infants.


Assuntos
Antineoplásicos/efeitos adversos , Desenvolvimento Fetal/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Aleitamento Materno , Neoplasias da Mama/tratamento farmacológico , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Neoplasias Ovarianas/cirurgia , Período Pós-Parto , Gravidez , Trimestres da Gravidez/efeitos dos fármacos
11.
Am J Obstet Gynecol ; 205(6): 535.e1-5, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21872200

RESUMO

OBJECTIVE: This study reports the gynecologic conditions in postmenopausal women (intact uterus on enrollment) in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study of tamoxifen and raloxifene (STAR)/P-2 trial. STUDY DESIGN: This study, with a median follow-up period of 81 months, evaluated the incidence rates/risks of gynecologic conditions among women who were treated with tamoxifen and raloxifene. RESULTS: Compared with women who received tamoxifen therapy, women who received raloxifene therapy had a lower incidence of uterine cancer (relative risk, 0.55)/endometrial hyperplasia (relative risk, 0.19), leiomyomas (relative risk, 0.55), ovarian cysts (relative risk, 0.60), and endometrial polyps (relative risk, 0.30) and had fewer procedures performed. Women receiving tamoxifen therapy had more hot flashes (P < .0001), vaginal discharge (P < .0001), and vaginal bleeding (P < .0001). CONCLUSION: Our results suggest that tamoxifen has more of an estrogenic effect on the gynecologic reproductive organs. These effects should be considered in counseling women on options for breast cancer prevention.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Leiomioma/epidemiologia , Cloridrato de Raloxifeno/uso terapêutico , Tamoxifeno/uso terapêutico , Neoplasias Uterinas/epidemiologia , Idoso , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/prevenção & controle , Hiperplasia Endometrial/epidemiologia , Hiperplasia Endometrial/prevenção & controle , Antagonistas de Estrogênios/uso terapêutico , Feminino , Seguimentos , Fogachos/epidemiologia , Humanos , Incidência , Leiomioma/prevenção & controle , Pessoa de Meia-Idade , Cistos Ovarianos/epidemiologia , Cistos Ovarianos/prevenção & controle , Pólipos/epidemiologia , Pólipos/prevenção & controle , Pós-Menopausa/efeitos dos fármacos , Fatores de Risco , Neoplasias Uterinas/prevenção & controle , Descarga Vaginal/epidemiologia
12.
Clin Breast Cancer ; 11(5): 332-41, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21729670

RESUMO

INTRODUCTION: Emerging research suggests a substantially greater prevalence of the adverse triple-negative (TN) subtype (human epidermal growth factor receptor [HER]2(-), estrogen receptor [ER](-), and progesterone receptor [PR])(-)) among black patients with breast cancer. No reports however have been generated from a statewide cancer registry. PATIENTS AND METHODS: The study consisted of all black patients (N = 643) and a random sample of white patients (n = 719) diagnosed with primary invasive breast cancer (2000-2003) listed in the National Cancer Institute-Surveillance Epidemiology and End Results (NCI-SEER) Connecticut Tumor Registry (CTR). HER2 status was obtained from pathology reports submitted to the registry. Remaining data were obtained from the registry database. RESULTS: TN tumors were more prevalent in black compared with white patients (30.8% vs. 11.2%, respectively; P < .001.) There was a 2-fold greater frequency of ER(-) and PR(-) phenotypes among black patients, but HER2 status did not differ by race. Patients with lobular cancer were less likely to have TN breast cancer compared with patients with ductal tumors (odds ratio [OR] = 0.23; 95% confidence interval [CI], 0.10-0.58). Among patients with regional disease, black patients exhibited increased risk of death (relative risk [RR] = 2.71; 95% CI, 1.48-4.97) independent of TN status. No survival disparity was found among patients with local disease. DISCUSSION: These registry-based data corroborate reports that TN breast cancer varies substantially by race and histologic subtype. A survival disparity among patients with advanced disease, but not local disease, casts some doubt on TN status as an explanation for differences. CONCLUSION: More research is warranted to understand why black patients with advanced breast cancer may be at increased risk for death whether or not their tumors express the TN phenotype.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/etnologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/epidemiologia , Carcinoma Lobular/etnologia , Carcinoma Lobular/patologia , Carcinoma Medular/epidemiologia , Carcinoma Medular/etnologia , Carcinoma Medular/patologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Programa de SEER , Análise de Sobrevida , Estados Unidos/epidemiologia
14.
Menopause ; 18(1): 17-22, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20689465

RESUMO

OBJECTIVE: The aim of this study was to establish the gynecological effects of 5 years of treatment with lasofoxifene versus placebo in postmenopausal osteoporotic women. METHODS: A total of 8,556 women aged 59 to 80 years with femoral neck or spine bone mineral density T scores of -2.5 or lower were randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or placebo, for 5 years. RESULTS: Endometrial cancer was confirmed for two women in each lasofoxifene group and for three women in the placebo group. Endometrial hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25 mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo), and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo, respectively. Lasofoxifene treatment resulted in a small increase in endometrial thickness versus placebo (least-squares mean change from baseline 1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and -0.72 mm for 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women required surgery for pelvic organ prolapse or urinary incontinence in the placebo and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group: 1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%, 5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene 0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively. CONCLUSION: These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women.


Assuntos
Pós-Menopausa/efeitos dos fármacos , Pirrolidinas/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tetra-Hidronaftalenos/efeitos adversos , Doenças Uterinas/diagnóstico por imagem , Útero/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Cistos Ovarianos/epidemiologia , Neoplasias Ovarianas/epidemiologia , Pólipos/diagnóstico por imagem , Pólipos/epidemiologia , Pólipos/patologia , Modelos de Riscos Proporcionais , Pirrolidinas/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico , Ultrassonografia , Incontinência Urinária/etiologia , Doenças Uterinas/epidemiologia , Doenças Uterinas/patologia , Útero/patologia
15.
Int J Gynecol Cancer ; 20(5): 772-80, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20973267

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of canfosfamide in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (OC). METHODS: Patients with platinum-refractory or -resistant (primary or secondary) OC were randomized to receive canfosfamide at 1000 mg/m² and PLD at 50 mg/m² intravenously or PLD alone at 50 mg/m2 intravenously on day 1 every 28 days until tumor progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). Other end points were objective response rate and safety. The study was originally planned for 244 patients. The trial was temporarily placed on hold after 125 patients were randomized while the results of another trial were being reviewed and the sponsor decided not to resume enrollment. The interim analysis became the final analysis. RESULTS: The median PFS was 5.6 months for canfosfamide + PLD (n = 65) versus 3.7 months for PLD (n = 60) (hazards ratio, 0.92; P = 0.7243). A preplanned subgroup analysis showed that 75 patients with platinum-refractory or primary platinum-resistant OC had a median PFS of 5.6 months for canfosfamide + PLD versus 2.9 months for PLD (hazards ratio, 0.55; P = 0.0425). Hematologic adverse events were 66% on the canfosfamide + PLD arm versus 44% on the PLD arm, manageable with dose reductions. Nonhematologic adverse events were similar for both arms. The incidence of palmar-plantar erythrodysesthesia and stomatitiswas lower on canfosfamide + PLD(23%, 31%, respectively) versus (39%, 49%, respectively) on PLD. CONCLUSIONS: Overall median PFS showed a positive trend but was not statistically significant. The median PFS in the platinum-refractory and primary platinum-resistant OC patients was significantly longer for canfosfamide + PLD versus PLD. Canfosfamide may ameliorate the palmar-plantar erythrodysesthesia and stomatitis known to be associated with PLD. Further study of this active well-tolerated regimen in platinum-refractory and primary platinum-resistant OC is planned. This study was registered at www.clinicaltrials.gov: NCT00350948.


Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Glutationa/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/administração & dosagem , Feminino , Glutationa/administração & dosagem , Humanos , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
Gynecol Oncol ; 119(3): 451-6, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20837357

RESUMO

BACKGROUND: The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response (pCR) at reassessment surgery in epithelial ovarian, fallopian tube, or primary peritoneal cancers (OFPC). METHODS: Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or, after histologic confirmation of diagnosis, neoadjuvantly. Treatment included paclitaxel (175 mg/m²) and carboplatin (AUC 6) every 3 weeks for up to 6 cycles, plus oral erlotinib 150 mg daily. The primary objective was to determine whether the pCR rate at reassessment surgery was at least 60% after optimal cytoreduction at initial surgery (< 1cm residual disease), or at least 40% after suboptimal cytoreduction (at least 1cm residual disease) using a two-stage design (alpha=0.10, beta=0.10). RESULTS: The study population included 56 patients with stage III-IV OFPC. EGFR gene amplification was present in 15% of the 20 tumors evaluated. Twenty-eight patients had protocol therapy after optimal cytoreduction (stratum I), 23 had protocol therapy either after suboptimal cytoreduction (stratum II), and 5 received neoadjuvant therapy prior to cytoreduction (stratum III). Pathologic CR was confirmed in 8 patients (29%; 95% confidence intervals 13%, 49%) in stratum I and 3 patients (11%, 95% C.I. 2%, 28%) in stratum II, which did not meet the prespecified efficacy endpoint in either stratum. CONCLUSIONS: Among unselected patients, erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Amplificação de Genes/efeitos dos fármacos , Genes erbB-1/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Adulto Jovem
17.
J Oncol Pract ; 6(3): 114-7, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20808551

RESUMO

Anecdotal information regarding clinical research sites limiting participation in NCI-funded cooperative group studies prompted ASCO to collect data on and investigate the reasons behind this trend.

18.
Cancer Prev Res (Phila) ; 3(6): 696-706, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20404000

RESUMO

The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.


Assuntos
Adenocarcinoma/prevenção & controle , Neoplasias da Mama/prevenção & controle , Estrogênios , Neoplasias Hormônio-Dependentes/prevenção & controle , Cloridrato de Raloxifeno/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Tamoxifeno/uso terapêutico , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Catarata/induzido quimicamente , Catarata/epidemiologia , Método Duplo-Cego , Uso de Medicamentos , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/epidemiologia , Feminino , Seguimentos , Fraturas Espontâneas/epidemiologia , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/prevenção & controle , Humanos , Incidência , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/prevenção & controle , Invasividade Neoplásica , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Hormônio-Dependentes/patologia , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/prevenção & controle , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/farmacologia , Risco , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/efeitos adversos , Tamoxifeno/farmacologia , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologia , Útero/patologia
19.
Gynecol Oncol ; 116(3): 442-6, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19931137

RESUMO

OBJECTIVE: Survival in women with recurrent or metastatic cervical cancer remains poor. More effective and less toxic regimens are needed. Cisplatin is an effective radiosensitizer, but its single agent activity in recurrent cervical cancer, especially after prior cisplatin exposure, is disappointing, with a response rate of only 13%. Oxaliplatin has preclinical activity in cisplatin-resistant tumors and may have synergic activity when combined with paclitaxel. Our objective is to determine the efficacy and toxicity of paclitaxel and oxaliplatin in patients with recurrent or metastatic cervical cancer. METHODS: Patients with histologic confirmation of primary metastatic or recurrent cervical cancer not amenable to surgical management were eligible. Treatment consisted of paclitaxel 175 mg/m(2) IV and oxaliplatin 130 mg/m(2) IV every 21 days. The primary endpoints were toxicity, recorded every cycle, and response, determined by RECIST criteria and were assessed every 9 weeks, with subsequent confirmation as required. Sample size determinations were made using a Simon's two-stage design with a projected overall response proportion of 13% with cisplatin alone. Survival rates were calculated with Kaplan-Meier methods. RESULTS: Of the 35 patients enrolled, 32 were evaluable. The median age was 56 (27-78); 30 had had prior radiation (23 concomitant with cisplatin). Patients completed a mean of 4.2 cycles (1-11). There were 2 complete and 5 partial responses for a total response rate of 7/32 (22%; 95% CI: 9.3%-40.0%). Eight patients had stable disease for an overall clinical benefit rate of 15/32 (47%; 95% CI: 29.1%-65.3%). The mean time to best response was 13.5 weeks (95% CI: 10.6, 16.4). The mean progression-free survival was 21 weeks (95% CI: 14.7, 27.2) and mean overall survival was 52 weeks (95% CI: 39.4, 64.8). A total of 135 cycles were administered. There were 28 (20.1%) grade 3/4 hematologic toxicities and 46 (34.1%) grade 3/4 non-hematologic toxicities, which were predominantly sensory neuropathy. There were 13 treatment delays, 4 dose reductions, and no treatment-related deaths. CONCLUSIONS: The combination of paclitaxel and oxaliplatin is an effective regimen in patients with recurrent or persistent cervical cancer including a majority previously exposed to cisplatin. Further study and comparison with other platinum-based regimens is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologia
20.
Womens Health (Lond) ; 5(6): 693-9, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19863472

RESUMO

One of the most challenging issues in gynecologic oncology is the high mortality rate of ovarian cancer, largely due to detection of disease in advanced stages. Women with early-stage disease have a significantly improved survival rate and may not require chemotherapy. Thus, the issues to examine are whether there are methods to improve early detection, thereby resulting in a reduction in mortality. Several large, randomized, clinical trials have recently completed evaluating CA 125 and transvaginal sonography as effective strategies to accomplish this goal. These issues and the results of the recent trials will be reviewed in this article.


Assuntos
Antígeno Ca-125/sangue , Programas de Rastreamento , Neoplasias Ovarianas/diagnóstico , Vagina/diagnóstico por imagem , Fatores Etários , Biomarcadores , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Ultrassonografia , Saúde da Mulher
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