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1.
AIDS Care ; 34(7): 926-935, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34612090

RESUMO

Little is known about how demographic, employment and meteorological factors impact physical activity. We conducted an analysis to explore these associations from participants (N = 447) from six cities in the United States and matched their activity data with abstracted local meteorological data from National Oceanic and Atmospheric Administration (NOAA) weather reports. Participants were purposively recruited in 3-month blocks, from December 2015 to October 2017, to reflect physical activity engagement across the seasons. We calculated total physical activity (minutes/week) based on 7-day physical activity recall. Mild correlations were observed between meteorological factors and correlated with lower physical activity. Participants were least active in autumn (Median = 220 min/week) and most active in spring (Median = 375 min/week). In addition to level of education and total hours of work, maximum temperature, relative humidity, heating degree day, precipitation and sunset time together explained 17.6% of variance in total physical activity. Programs assisting in employment for PLHIV and those that promote indoor physical activity during more strenuous seasons are needed. Additional research to better understand the selection, preferences, and impact of indoor environments on physical activity is warranted.


Assuntos
Infecções por HIV , Cidades , Exercício Físico , Infecções por HIV/epidemiologia , Humanos , Estações do Ano , Tempo (Meteorologia)
2.
AIDS Care ; 33(4): 434-440, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32005080

RESUMO

Social media tools have been touted as an approach to bring more democratic communication to health care. We conducted a multi-site cross-sectional study among persons living with HIV (PLWH) to desrcibe technology use among PLWH in the US and the association between social media use and body-mass index (BMI). Our primary predictor variable was social media use. Our primary outcome was BMI measured through height and weight. Descriptive statistics were used to describe the demographic profiles of the study participants and linear regression models were used to analyze associations between the outcome and predictor variables controlling for demographic characteristics. Study participants (N = 606) across 6 study sites in the United States were predominately 50-74 years old (67%). Thirty-three percent of study participants had a normal weight (BMI 18.5-25), 33% were overweight (BMI 25-30), and 32% were obese (BMI > 30). Participants used several social media sites with Facebook (45.6%) predominating. Social media use was associated with higher BMI in study participants (p < .001) and this effect persisted, although not as strongly, when limiting the analysis to those who only those who used Facebook (p = .03). Further consideration of social factors that can be ameliorated to improve health outcomes is timely and needed.


Assuntos
Índice de Massa Corporal , Infecções por HIV/psicologia , Mídias Sociais/estatística & dados numéricos , Adulto , Idoso , Peso Corporal , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Comportamento Sedentário , Estados Unidos/epidemiologia
3.
J Nurs Scholarsh ; 52(2): 183-191, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31804774

RESUMO

PURPOSE: This article aims to provide perspectives on the establishment of a consortium for nurse scientists with similar career trajectories interested in cancer-related symptoms (CRS) research. Hereby, we describe the development of and recent outcomes from the CRS consortium, the lessons learned in establishing the consortium, and future directions to advance the science of CRS. MODEL AND METHODS: New and innovative strategies are needed to address the complexity of CRS research. A CRS consortium was created to allow a mechanism for oncology nurse scientists with varying expertise to collaborate to advance CRS research. The National Institutes of Health (NIH) Symptom Science Model (SSM) guides the research of the CRS Consortium. DISCUSSION AND CONCLUSIONS: A need for improved CRS assessment and management has been identified. The CRS consortium was created as a collaborative think tank to begin to address this need. Guided by the NIH SSM, CRS consortium members have worked to define symptom phenotypes, enhance understanding of the biologic mechanisms that can contribute to symptom phenotypes, and develop tailored interventions to improve symptom management. Dissemination of the CRS consortium efforts involve publications and presentations. CLINICAL IMPLICATIONS: Nurse scientists interested in symptom science and biobehavorial research face many challenges on how to initiate and sustain independent programs of research. Through the formation of a CRS consortium, oncology nurse scientists can work together to address identified issues in symptom measurement and management.


Assuntos
Neoplasias/enfermagem , Pesquisa em Enfermagem/organização & administração , Enfermagem Oncológica/organização & administração , Cuidados Paliativos/organização & administração , Medicina de Precisão/métodos , Avaliação de Sintomas/métodos , Estudos de Associação Genética , Humanos , Modelos Organizacionais , Neoplasias/diagnóstico , Desenvolvimento de Programas
4.
J Adv Pract Oncol ; 10(1): 24-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308986

RESUMO

Exercise is recommended for cancer survivors, as it mitigates treatment side effects and improves overall wellness. Therefore, survivors attend community-based exercise programs and report positive results, but published evaluations of outcomes of these programs are scarce in the literature. The objective of this study is to validate the anecdotal reports of the physical fitness and quality of life benefits of the LIVESTRONG at the YMCA program. A retrospective analysis of deidentified data consisting of 17 program cohorts of the LIVESTRONG at the YMCA program (n = 88) was conducted. Statistically significant improvements were seen when compared to baseline in the physical fitness measures of the 6-minute walk, the chest and leg presses, the sit-and-reach test, and the one-leg stand test, as well as in the domains of the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) Profile, a health-related quality of life questionnaire. These domains are physical function, anxiety, depression, fatigue, social role satisfaction, and pain. The anecdotal impression that participation in the LIVESTRONG at the YMCA program improves physical fitness and subjective quality of life perceptions was supported by statistical analysis of the subjective and objective pre- and postprogram measurements for this data set. Exercise in this cancer-specific community exercise program is likely to improve physical fitness and quality of life outcomes.

5.
J Cardiovasc Nurs ; 34(5): 364-371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31343620

RESUMO

BACKGROUND: People living with human immunodeficiency virus (PLHIV) are at an increased risk for developing cardiovascular disease (CVD). Physical activity and cardiorespiratory fitness in PLHIV are poorly understood. OBJECTIVE: The aims of this study were to describe physical activity and cardiorespiratory fitness by sex and age and to examine the association between physical activity and cardiorespiratory fitness in PLHIV, controlling for covariates. METHODS: Seven hundred two PLHIV participated in a cross-sectional study and completed validated measures of self-reported physical activity (7-day Physical Activity Recall) and cardiorespiratory fitness (6-minute walk test). Participants were recruited from 7 diverse sites in the United States and Thailand, and data were analyzed using descriptive statistics and multiple regression to examine the relationship between physical activity and cardiorespiratory fitness. RESULTS: On average, participants self-reported engaging in 115 minutes of, mostly light (75%), physical activity. Men reported twice the amount of physical activity as women (155 vs 73 minutes, P = .01). Participants' ability to achieve their predicted 6-minute walk test distances was similar between men (68%) and women (69%) (P > .01). For women, vigorous physical activity was associated with a 6.6% increase in cardiorespiratory fitness and being temporarily unemployed was associated with an 18% decline in cardiorespiratory fitness. Cardiorespiratory fitness increased with age (P < .01). CONCLUSIONS: Weekly physical activity of people living with human immunodeficiency virus averaged 85 minutes of mostly light activity, well below the recommended 150 minutes of moderate activity. Vigorous physical activity was associated with improved cardiorespiratory fitness in women, but not men. Although PLHIV would benefit from interventions to increase physical activity, our data suggest a need to develop sex-specific physical activity strategies.


Assuntos
Aptidão Cardiorrespiratória , Exercício Físico , Infecções por HIV/epidemiologia , Fatores Etários , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Fatores Sexuais , Tailândia/epidemiologia , Estados Unidos/epidemiologia , Teste de Caminhada
6.
West J Nurs Res ; 40(6): 815-833, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28322649

RESUMO

The study tested the feasibility and efficacy of an exergaming program in underserved older African American communities. The study is a single-group with pre- and posttest design. Twelve female participants ( M age = 64.17 ± 6.74 years) completed an exergaming program once or twice a week for 24 sessions over 14 weeks. Community health workers implemented the program through coaching and supporting mechanisms to motivate participants to exercise. A mixed-methods analysis was used to assess the intervention. After the program, participants showed significant improvements in lower body flexibility ( p = .012), and physical health-related quality of life ( p = .005). Four themes were identified related to the self-reported benefits of the exergaming program: (a) improving health, (b) feeling enjoyment, (c) getting connected, and (d) knowing you. The exergaming program provides an easy-to-implement and potentially effective intervention that can be used in community-directed centers to improve health and well-being in the underserved population.


Assuntos
Negro ou Afro-Americano/psicologia , Agentes Comunitários de Saúde/psicologia , Exercício Físico , Avaliação de Programas e Projetos de Saúde/métodos , Autorrelato , Estudos de Viabilidade , Feminino , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Vida Independente , Pessoa de Meia-Idade , Qualidade de Vida , Populações Vulneráveis
7.
Clin J Oncol Nurs ; 20(6 Suppl): S2, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27857271

RESUMO

Thirty years ago, the first article on exercise for patients with cancer appeared in the cancer research literature. The time from that first article to the present has included oncology nurses taking the lead in investigations related to exercise and cancer-related symptoms, most notably cancer-related fatigue (CRF). The Oncology Nursing Society (ONS) has been instrumental in publishing much of the research on exercise and cancer and continues in that tradition by issuing this supplement to the Clinical Journal of Oncology Nursing. In addition, ONS has facilitated the translation of research findings to practicing oncology nurses by convening meetings, participating in expert opinion consensus groups, and disseminating evidence through Putting Evidence Into Practice resources.


Assuntos
Exercício Físico/fisiologia , Neoplasias/enfermagem , Enfermagem Oncológica/métodos , Qualidade de Vida , Enfermagem Baseada em Evidências , Fadiga/prevenção & controle , Fadiga/terapia , Feminino , Humanos , Masculino , Neoplasias/diagnóstico , Sociedades de Enfermagem , Sobreviventes
8.
Clin J Oncol Nurs ; 20(6 Suppl): S25-S30, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27857276

RESUMO

BACKGROUND: Cancer exercise programming in the community has been emerging in response to the increasing numbers of cancer survivors and social factors favoring movement away from a sedentary lifestyle. OBJECTIVES: This article examines several community-based exercise programs for cancer survivors as exemplars of successful programs. METHODS: The article investigates where the research is leading as technological advances and cloud-based technologies change the fitness landscape. Links to valuable resources for healthcare providers interested in current physical activity recommendations for cancer survivors are also offered. FINDINGS: Accumulating evidence suggests that cancer survivors who engage in an active lifestyle have less fatigue, better quality of life, improved sense of well-being, and, in the case of breast and colon cancers, a reduced risk of recurrent disease.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Terapia por Exercício/organização & administração , Neoplasias/psicologia , Neoplasias/reabilitação , Qualidade de Vida , Sobreviventes/psicologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Aptidão Física/fisiologia , Avaliação de Programas e Projetos de Saúde
9.
Nurs Manag (Harrow) ; 22(2): 24-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25921908

RESUMO

Patient care visibility technology systems provide real-time information about patient admissions, discharges, transport, clinical activities and housekeeping services, in order to enhance patient care and flow. This article reports the results of a descriptive study that explored healthcare professionals' perceptions of and attitudes to a patient care visibility technology system in an acute care setting. The results indicate that staff find the system user friendly, and are positive about its staff- and patient-focused characteristics. Overall, positive staff perceptions and acceptance imply positive use of the system. This study forms the basis for further research on the effects on the patient-care outcomes of healthcare professionals' use of these systems.


Assuntos
Atitude do Pessoal de Saúde , Enfermagem de Cuidados Críticos/organização & administração , Pessoal de Saúde , Arquitetura Hospitalar , Monitorização Fisiológica/enfermagem , Postos de Enfermagem , Qualidade da Assistência à Saúde/organização & administração , Estudos Transversais , Humanos , Estudos Prospectivos , Inquéritos e Questionários
10.
Nurs Adm Q ; 36(3): 217-24, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22677962

RESUMO

Nursing leadership at Morristown Medical Center, a Magnet-designated, 600-plus bed tertiary care center, in response to forces, such as health care reform, and recommendations, such as those outlined in the Institute of Medicine report The Future of Nursing, developed an innovative model of care delivery called the Partners in Caring. This model of care delivery is an approach built on a functional unit of registered nurse-nurse assistant partnership supported by a patient care facilitator. The nursing partners are accountable for the coordination of patient care with an emphasis on patient and organizational goal achievement of (1) improving the health of our patients, (2) developing and maintaining an improved and responsive health care system, and (3) lowering costs while delivering quality care. The model of care was developed and is being implemented and evaluated using a knowledge translation methodology to ensure its evidence base and outcome achievement. Transforming workforce roles and communication patterns, incorporating technology to benefit time management and maintaining a keen focus on achieving patient outcomes are hallmarks of this new model.


Assuntos
Comportamento Cooperativo , Atenção à Saúde/métodos , Difusão de Inovações , Enfermagem Baseada em Evidências/métodos , Modelos de Enfermagem , Benchmarking , Grupos Focais , Humanos , Liderança , Modelos Organizacionais , Projetos Piloto , Estados Unidos
11.
Med Sci Sports Exerc ; 44(2): 352-61, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21796050

RESUMO

PURPOSE: This study, theoretically based on the Exercise Self-Esteem Model, EXSEM, examined effects of exercise modality on physical and global self-esteem (PSE, GSE) in breast cancer survivors. The EXSEM posits GSE at the apex with PSE feeding into GSE. PSE has three subdomains: physical condition (PC), attractive body (AB), and physical strength (PS). The goals were to compare the effect of combination modality versus single-modality exercise on PSE and GSE and to explore the relationship between exercise modality and the subdomains of PSE. METHODS: Survivors were randomly allocated to flexibility (F), aerobic (A), resistance (R), or aerobic plus resistance (AR), 12-wk, individualized, home-based exercise program. Pre/posttesting included submaximal treadmill test, six-repetition maximum chest press and leg press, YMCA bench press, shoulder/hip flexibility, and bioelectric impedance analysis body composition. Esteem measures were the Physical Self-Perception Profile and the Rosenberg Self-Esteem Scale. RESULTS: Forty-two women completed the study (F = 12, A = 10, R = 9, and AR = 11). Fitness improvements congruent with exercise modality were seen in all groups. PSE and GSE outcomes did not reveal a greater effect from the combination modality program, AR, compared with the single-modality programs A and R. The relationships between the single-modality groups and the subdomains of PC, PS, and AB were supported in the R group (PS and AB increased) and were partially supported in the A group (PC, not AB, increased). CONCLUSIONS: A single-modality R program significantly improved all domains of PSE, and participation in the A program improved the PC subdomain. The combination exercise program did not enhance PSE greater than the single-modality programs. EXSEM was a useful framework for exploring esteem in breast cancer survivors.


Assuntos
Neoplasias da Mama/psicologia , Exercício Físico/psicologia , Autoimagem , Adulto , Composição Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Aptidão Física/psicologia , Treinamento Resistido/métodos , Sobreviventes/psicologia , Levantamento de Peso/psicologia
12.
Semin Oncol Nurs ; 23(4): 285-96, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18022056

RESUMO

OBJECTIVE: To review the evidence of the effects of exercise interventions in patients with cancer in each of four quality-of-life domains: physical, psychological, social, and spiritual. DATA SOURCES: Research articles, abstracts, literature review. CONCLUSION: There is strong evidence to support positive effects of exercise on physical and psychological well-being. Exercise improves physical function, muscle strength, emotional well-being, self esteem, decreases fatigue, anxiety, and depression, and helps maintain weight. Data suggest exercise fosters social functioning and more research is needed on the relationship of exercise and spiritual well-being. IMPLICATIONS FOR NURSING PRACTICE: There is sufficient evidence to support exercise as an intervention to enhance a cancer patient's physical functioning and psychological well-being. Nurses should be encouraged to integrate physical activity recommendations into practice, tailored to the individual's health condition and mutual goal setting.


Assuntos
Exercício Físico , Neoplasias/fisiopatologia , Qualidade de Vida , Humanos
13.
Med Sci Monit ; 9(8): PI99-104, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12942041

RESUMO

BACKGROUND: Marimastat is a potent inhibitor of matrix metalloproteinases and in preclinical studies enhances the anti-tumor activity of certain chemotherapeutics. We performed a phase I clinical evaluation of the combination of oral marimastat and intravenous paclitaxel, to determine if these drugs could be co-administered safely, and to determine whether marimastat alters paclitaxel pharmacokinetics. MATERIAL/METHODS: Marimastat was administered twice daily and paclitaxel as a three hour infusion every three weeks. Doses of both marimastat and paclitaxel were escalated in cohorts of patients up to maximal doses of 10 mg for marimastat and 175 mg/m2 for paclitaxel. Paclitaxel plasma pharmacokinetic parameters were assessed in the absence (cycle 1) and presence (cycle 2) of marimastat. Trough marimastat plasma levels were evaluated during cycle 2. RESULTS: A total of 19 patients were treated at three different dose levels. There were no dose-limiting toxicities during the first cycle of therapy, resulting in dose escalation up to the planned maximal dose for each drug. Neutropenia was the most common significant toxicity at the highest dose level, with grade 3 or higher neutropenia occurring in 38% of patients. There were no complete or partial responses. Pharmacokinetic analyses indicate that marimastat does not alter paclitaxel clearance. At the 10 mg dose, the mean trough marimastat level was 14.8 Kg/L. CONCLUSIONS: Marimastat and paclitaxel can be co-administered safely at doses equivalent to those recommended for single-agent administration. Additional studies are necessary to determine whether this combination is more effective in controlling tumor progression than paclitaxel alone.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores Enzimáticos/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Adulto , Idoso , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Feminino , Humanos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/farmacocinética , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Paclitaxel/química , Paclitaxel/farmacocinética
14.
Clin Cancer Res ; 9(7): 2504-9, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12855624

RESUMO

PURPOSE: Resistance to topoisomerase (TOP) 1 and 2 inhibitors is a potentially important reason for treatment failure, and may be related, in part, to a down-regulation of the specific TOP target. Investigators in our laboratories previously noted such a down-regulation of the target, along with a reciprocal up-regulation of the alternate TOP. Therefore, sequencing TOP inhibitors may provide a means for overcoming resistance to the TOP I and II inhibitors. Furthermore, point mutations in TOP I, which confer resistance to TOP I inhibitors, were associated with collateral sensitivity to cisplatin. EXPERIMENTAL DESIGN: A dose escalating Phase I trial of topotecan (at doses of 0.75 to 1.0 mg/m(2)/day) on days 1 to 3 with etoposide (70-80 mg/m(2)/day) and cisplatin (20-25 mg/m(2)/day) on days 8 to 10. The timing of the drug sequence was based on the prior Phase I pharmacokinetic and pharmacodynamic studies of camptothecin and etoposide, and the level of the TOP targets in peripheral blood monocytes. RESULTS: Fifteen patients (7 males and 8 females) received 40 courses of therapy across three dose levels. The median age was 56 (range, 39-77), and the median performance status was 1 (range, 0-2). The diagnoses included: non-small cell lung cancer (7), head and neck cancer (2), cancer of unknown primary (2), and 1 each of ovarian cancer, prostate cancer, gastric cancer, and renal cancer. Level 1 (topotecan 1.0 mg/m(2)/day; etoposide 80 mg/m(2)/day; and cisplatin 25 mg/m(2)/day) produced severe and prolonged febrile neutropenia in the first patient treated, and the subsequent patients were then entered onto a reduced dose level (cohort 2: topotecan 0.75 mg/m(2)/day; etoposide 70 mg/m(2)/day; and cisplatin 20 mg/m(2)/day). Three of 6 patients on cohort 2 experienced grade IV neutropenia >5 days, and a decision was then made to add filgrastim at 5 micro g/kg rather than additionally reduce the dosages (cohort 3). Eight patients were then treated on cohort 3, and 1 of the 8 patients experienced a grade 4 neutropenia. Thus, cohort level three was considered the recommended dose for Phase II studies. Twelve of the 15 patients had disease assessable for response to therapy. Seven achieved stable disease for >/==" BORDER="0">2 months, whereas 5 showed continued progression of their disease. CONCLUSIONS: These data show that sequencing TOP 1 and 2 inhibitors is feasible, and topotecan 0.75 mg/m(2)/day days 1-3; etoposide 70 mg/m(2)/day days 8-10; and cisplatin 20 mg/m(2)/day days 8-10 with filgrastim at 5 micro g/kg is an appropriate dose and schedule to test the concept of modulating TOP levels by sequencing the administration of the respective TOP inhibitors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Neoplasias/tratamento farmacológico , Inibidores da Topoisomerase I , Inibidores da Topoisomerase II , Topotecan/administração & dosagem , Adulto , Idoso , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
15.
Clin Cancer Res ; 9(5): 1673-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12738720

RESUMO

PURPOSE: To investigate pharmacologically guided addition of etoposide to a weekly irinotecan/cisplatin chemotherapy. PATIENTS AND METHODS: Patients with advanced nonhematologic malignancies were eligible. Treatment consisted of i.v. administration of 50 mg/m(2) irinotecan and 20 mg/m(2) cisplatin on days 1, 8, 15, and 22 of a 42-day cycle or on days 1 and 8 of a 21-day cycle. Etoposide was administered in a dose-escalating fashion 2 days after each dose of irinotecan/cisplatin, either i.v. as a single dose or p.o. as two doses administered 12 h apart. Pharmacologic analyses included measurement of plasma concentrations of irinotecan, SN-38, and SN-38 glucuronide, as well as quantitation of topoisomerase protein levels in peripheral blood mononuclear cells (PBMNCs). RESULTS: A total of 40 patients with a variety of malignancies received 122 cycles of therapy. Dose-limiting toxicities included neutropenia and diarrhea, with the 21-day cycle tolerated better than the 42-day cycle. For the 21-day cycle, the maximum tolerated dose was 75 mg/m(2) for i.v. etoposide and 85 mg/m(2) for oral etoposide. Objective responses were observed in four patients with previously treated mesothelioma, gastric, breast, and ovarian cancer, respectively. PBMNC levels of topoisomerase IIalpha were increased at the time of etoposide administration in two patients, with these patients having the highest SN-38 glucuronide peak-plasma-concentration and area-under-the-curve values among 15 patients with available pharmacokinetic data. One of these patients had a partial response to therapy. CONCLUSIONS: Pharmacologically guided administration of etoposide in combination with irinotecan/cisplatin using a 21-day cycle is associated with acceptable toxicity and significant antitumor activity. The finding that PBMNC topoisomerase IIalpha protein levels increased after irinotecan/cisplatin treatment in two of six patients supports the continued development of sequential topoisomerase targeting in the treatment of malignancy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias/tratamento farmacológico , Inibidores da Topoisomerase I , Inibidores da Topoisomerase II , Adulto , Idoso , Antígenos de Neoplasias/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Camptotecina/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , DNA Topoisomerases Tipo I/sangue , DNA Topoisomerases Tipo II/sangue , Proteínas de Ligação a DNA , Etoposídeo/administração & dosagem , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/sangue
16.
Clin Cancer Res ; 8(12): 3710-7, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12473580

RESUMO

PURPOSE: The purpose of this study was to investigate the safety and tolerability of Zosuquidar.3HCl, a potent inhibitor of P-glycoprotein (Pgp), when administered p.o. alone and in combination with doxorubicin and to determine whether Zosuquidar.3HCl affects doxorubicin pharmacokinetics and inhibits Pgp function in peripheral blood natural killer lymphocytes. EXPERIMENTAL DESIGN: Patients with advanced nonhematological malignancies were eligible for this Phase I trial. Zosuquidar.3HCl and doxorubicin were administered separately during the first cycle of therapy and then administered concurrently. Zosuquidar.3HCl was administered over 4 days, with doses escalated until the occurrence of dose-limiting toxicity. Subsequently, doxorubicin doses were increased from 45 to 75 mg/m(2). Zosuquidar.3HCl, doxorubicin, and doxorubicinol pharmacokinetics were analyzed, and dual fluorescence cytometry was used to determine the effects of Zosuquidar.3HCl on Pgp function in natural killer cells. RESULTS: A total of 38 patients were treated at nine dose levels. Neurotoxicity was dose-limiting for oral Zosuquidar.3HCl, characterized by cerebellar dysfunction, hallucinations, and palinopsia. The maximum-tolerated dose for oral Zosuquidar.3HCl administered every 12 h for 4 days is 300 mg/m(2). Zosuquidar.3HCl did not affect doxorubicin myelosuppression or pharmacokinetics, and Zosuquidar.3HCl pharmacokinetics were similar in the absence and presence of doxorubicin. Higher plasma concentrations of Zosuquidar.3HCl were associated with greater Pgp inhibition in natural killer cells. CONCLUSION: Zosuquidar.3HCl can be coadministered with doxorubicin using a 4-day oral dosing schedule, with little effect on doxorubicin toxicity or pharmacokinetics. Further refinement in Zosuquidar.3HCl dosing and scheduling should be explored to optimize Pgp inhibition while minimizing cerebellar toxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Administração Oral , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Doenças Cerebelares/induzido quimicamente , Dibenzocicloeptenos/administração & dosagem , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/patologia , Quinolinas/administração & dosagem
17.
Cancer Chemother Pharmacol ; 50(1): 80-3, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12111116

RESUMO

PURPOSE: Gemcitabine and cisplatin are routinely used in combination. In this combination, gemcitabine at conventional doses of 1000-1500 mg/m(2) is delivered weekly as a 30-minute bolus. Laboratory data suggest that the synthesis of gemcitabine triphosphate is saturable, and that gemcitabine infused at a rate of 10 mg/m(2) per min optimizes accumulation of the triphosphate. Early clinical experience suggests that gemcitabine delivered by a more prolonged infusion is more myelosuppressive. In this pilot study, we wished to assess if full-dose gemcitabine when given with cisplatin could be delivered by this more prolonged infusion. METHODS: In this study, all patients received cisplatin 75 mg/m(2). All gemcitabine doses were delivered at 10 mg/m(2) per min. For the initial cohort (level 1) the gemcitabine dose was 800 mg/m(2) per min. Subsequent escalations were 1000 mg/m(2) per min (level 2), and 1250 mg/m(2) per min (levels 3 and 4). For the first three cohorts, patients received gemcitabine on days 1, 8, and 15 and cisplatin on day 15 on a 28-day cycle. Patients on level 4 received gemcitabine on days 1 and 8 and cisplatin on day 8 on a 21-day cycle. Dose omissions or delays (holds) were mandated for NCI CTC grade 3 or 4 granulocytopenia or grade 2-4 thrombocytopenia. RESULTS: Entered onto this dose-finding study were 23 patients (12 male, 11 female) with advanced solid tumors. Seven patients were treatment-naive. Six patients were treated on level 1, five each on levels 2 and 3 and seven on level 4. Patients received one to seven cycles of treatment. Myelosuppression-related dose holds occurred at all levels. First-cycle dose holds occurred in three of six, four of five, three of five and two of seven patients on successive levels. First-cycle grade 3 or 4 granulocytopenia/thrombocytopenia occurred in three patients on level 1, one patient on level 2, two patients on level 3 and three patients on level 4. There were no partial or complete responses. Four patients were removed for toxicity (three myelosuppression, one nephrotoxicity), one at physician discretion, and 15 with disease progression. Three patients stopped therapy with stable disease after 5-6 months. On level 3, three of five patients remained on therapy for 4 months or more, compared to only one patient on each of the other three levels. CONCLUSIONS Weekly gemcitabine 1250 mg/m(2), utilizing a 10 mg/m(2) per min infusion rate, can be delivered with cisplatin 75 mg/m(2) with tolerable toxicity. When used in combination with cisplatin, however, the benefit of this fixed dose rate infusion gemcitabine compared to standard bolus gemcitabine remains to be determined.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Gencitabina
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