RESUMO
Background: Shared decision-making at end of life (eol) requires discussions about goals of care and prioritization of length of life compared with quality of life. The purpose of the present study was to describe patient and oncologist discordance with respect to goals of care and to explore possible predictors of discordance. Methods: Patients with metastatic cancer and their oncologists completed an interview at study enrolment and every 3 months thereafter until the death of the patient or the end of the study period (15 months). All interviewees used a 100-point visual analog scale to represent their current goals of care, with quality of life (scored as 0) and survival (scored as 100) serving as anchors. Discordance was defined as an absolute difference between patient and oncologist goals of care of 40 points or more. Results: The study enrolled 378 patients and 11 oncologists. At baseline, 24% discordance was observed, and for patients who survived, discordance was 24% at their last interview. For patients who died, discordance was 28% at the last interview before death, with discordance having been 70% at enrolment. Dissatisfaction with eol care was reported by 23% of the caregivers for patients with discordance at baseline and by 8% of the caregivers for patients who had no discordance (p = 0.049; Ï = 0.20). Conclusions: The data indicate the presence of significant ongoing oncologist-patient discordance with respect to goals of care. Early use of a simple visual analog scale to assess goals of care can inform the oncologist about the patient's goals and lead to delivery of care that is aligned with patient goals.
Assuntos
Neoplasias , Oncologistas , Relações Médico-Paciente , Assistência Terminal , Adulto , Idoso , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Qualidade de VidaRESUMO
BACKGROUND: Sunitinib is approved worldwide for treatment of advanced pancreatic neuroendocrine tumours (pNET), but no validated markers exist to predict response. This analysis explored biomarkers associated with sunitinib activity and clinical benefit in patients with pNET and carcinoid tumours in a phase II study. METHODS: Plasma was assessed for vascular endothelial growth factor (VEGF)-A, soluble VEGF receptor (sVEGFR)-2, sVEGFR-3, interleukin (IL)-8 (n=105), and stromal cell-derived factor (SDF)-1α (n=28). Pre-treatment levels were compared between tumour types and correlated with response, progression-free (PFS), and overall survival (OS). Changes in circulating myelomonocytic and endothelial cells were also analysed. RESULTS: Stromal cell-derived factor-1α and sVEGFR-2 levels were higher in pNET than in carcinoid (P=0.003 and 0.041, respectively). High (above-median) baseline SDF-1α was associated with worse PFS, OS, and response in pNET, and high sVEGFR-2 with longer OS (P⩽0.05). For carcinoid, high IL-8, sVEGFR-3, and SDF-1α were associated with shorter PFS and OS, and high IL-8 and SDF-1α with worse response (P⩽0.05). Among circulating cell types, monocytes showed the largest on-treatment decrease, particularly CD14+ monocytes co-expressing VEGFR-1 or CXCR4. CONCLUSIONS: Interleukin-8, sVEGFR-3, and SDF-1α were identified as predictors of sunitinib clinical outcome. Putative pro-tumorigenic CXCR4+ and VEGFR-1+ monocytes represent novel candidate markers and biologically relevant targets explaining the activity of sunitinib.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Citocinas/sangue , Indóis/uso terapêutico , Monócitos/patologia , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/tratamento farmacológico , Pirróis/uso terapêutico , Biomarcadores Tumorais/imunologia , Tumor Carcinoide/sangue , Tumor Carcinoide/tratamento farmacológico , Tumor Carcinoide/imunologia , Citocinas/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Monócitos/imunologia , Tumores Neuroendócrinos/imunologia , Sunitinibe , Resultado do TratamentoRESUMO
Patient participation in cancer clinical trials is low. Little is known about attitudinal barriers to participation, particularly among patients who may be offered a trial during an imminent initial oncology consult. The aims of the present study were to confirm the presence of proposed subscales of a recently developed cancer clinical trial attitudinal barriers measure, describe the most common cancer clinical trials attitudinal barriers, and evaluate socio-demographic, medical and financial factors associated with attitudinal barriers. A total of 1256 patients completed a survey assessing demographic factors, perceived financial burden, prior trial participation and attitudinal barriers to clinical trials participation. Results of a factor analysis did not confirm the presence of the proposed four attitudinal barriers subscale/factors. Rather, a single factor represented the best fit to the data. The most highly-rated barriers were fear of side-effects, worry about health insurance and efficacy concerns. Results suggested that less educated patients, patients with non-metastatic disease, patients with no previous oncology clinical trial participation, and patients reporting greater perceived financial burden from cancer care were associated with higher barriers. These patients may need extra attention in terms of decisional support. Overall, patients with fewer personal resources (education, financial issues) report more attitudinal barriers and should be targeted for additional decisional support.
Assuntos
Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/psicologia , Participação do Paciente/psicologia , Idoso , Ensaios Clínicos como Assunto , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Participação do Paciente/economia , Participação do Paciente/estatística & dados numéricos , Encaminhamento e Consulta , Inquéritos e QuestionáriosRESUMO
BACKGROUND: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. METHODS: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375-1000 mg/m(2) b.i.d.) for 14 days every 21 days. Radioembolization with (90)Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. RESULTS: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m(2). The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. CONCLUSIONS: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m(2) b.i.d. is recommended for phase II study with sequential lobar radioembolization.
Assuntos
Desoxicitidina/análogos & derivados , Embolização Terapêutica/métodos , Fluoruracila/análogos & derivados , Neoplasias/terapia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Estudos de Coortes , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Dose Máxima Tolerável , Microesferas , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Estudos ProspectivosRESUMO
BACKGROUND: We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. PATIENTS AND METHODS: Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥ 10 ng/ml and CEA measurements within ± 30 days of the CTC collection were included. RESULTS: We included 217 patients with mCRC who had a CEA value of ≥ 10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥ 25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥ 3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. CONCLUSIONS: This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.
Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais , Células Neoplásicas Circulantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Sobrevida , Adulto JovemRESUMO
BACKGROUND: Cancer clinical trials (CCTs) are important tools in the development of improved cancer therapies; yet, participation is low. Key psychosocial barriers exist that appear to impact a patient's decision to participate. Little is known about the relationship among knowledge, self-efficacy, preparation, decisional conflict, and patient decisions to take part in CCTs. OBJECTIVE: The purpose of this study was to determine if preparation for consideration of a CCT as a treatment option mediates the relationship between knowledge, self-efficacy, and decisional conflict. We also explored whether lower levels of decisional conflict are associated with greater likelihood of CCT enrollment. METHOD: In a pre-post test intervention study, cancer patients (N = 105) were recruited before their initial consultation with a medical oncologist. A brief educational intervention was provided for all patients. Patient self-report survey responses assessed knowledge, self-efficacy, preparation for clinical trial participation, decisional conflict, and clinical trial participation. RESULTS: Preparation was found to mediate the relationship between self-efficacy and decisional conflict (p = 0.003 for a test of the indirect mediational pathway for the decisional conflict total score). Preparation had a more limited role in mediating the effect of knowledge on decisional conflict. Further, preliminary evidence indicated that reduced decisional conflict was associated with increased clinical trial enrollment (p = 0.049). CONCLUSIONS: When patients feel greater CCT self-efficacy and have more knowledge, they feel more prepared to make a CCT decision. Reduced decisional conflict, in turn, is associated with the decision to enroll in a clinical trial. Our results suggest that preparation for decision-making should be a target of future interventions to improve participation in CCTs.
Assuntos
Ensaios Clínicos como Assunto/psicologia , Conflito Psicológico , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias/terapia , Autoeficácia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Seleção de PacientesRESUMO
BACKGROUND: Increased Aurora kinase A gene copy number (AURKA-CN) has been reported in metastatic colorectal cancer (mCRC), with unknown relationship to clinical outcome. We correlated increased AURKA-CN in mCRC tumours with KRAS mutation status, overall and progression-free survival (OS, PFS). METHODS: Sixty-one mCRC tumours were analysed for AURKA-CN using q-PCR, and KRAS mutation status by direct sequencing. Expression of AURKA protein was analysed by immunohistochemistry. Cox-proportional hazard method, Kaplan-Meier curves and log-rank statistics were used to estimate and compare the hazard ratios and median survival between the groups. RESULTS: In all, 68% of tumour exhibited high AURKA-CN, and 29% had a KRAS mutation, without correlation between the two. Patients with high AURKA-CN tumours had longer median OS (48.6 vs 18.8 months, P=0.01), with stronger trend among KRAS wild-type tumours (median OS not reached vs 18.8 months, P=0.003). Progression-free survival was longer on first-line or second-line chemotherapy among patients with KRAS wild-type and high vs low AURKA-CN (first: 17.6 vs 5.13 months, P=0.04; second: 10.4 vs 5.1 months, P=0.01). AURKA-CN level did not affect outcomes among patients with KRAS mutant tumours. CONCLUSION: Increased AURKA-CN is common in mCRC tumours and is associated with longer OS and longer PFS during chemotherapy, particularly in KRAS wild-type tumours.
Assuntos
Neoplasias Colorretais/genética , Dosagem de Genes , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aurora Quinase A , Aurora Quinases , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)RESUMO
BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIENTS AND METHODS: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of > or = 3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), >/=65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. CONCLUSION: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.
Assuntos
Neoplasias Colorretais/patologia , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Bevacizumab , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Valor Preditivo dos Testes , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
AIM: Patients with untreated advanced colorectal cancer were enrolled to this single arm phase II multi-center cooperative group trial of bevacizumab combined with IFL. The first 20 patients received irinotecan (125 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and leucovorin (20 mg/m(2)) weekly for four of six weeks and high-dose bevacizumab (10 mg/kg) every other week. Following a toxicity review of other trials using IFL, subsequent patients were enrolled at reduced doses of irinotecan (100 mg/m(2)) and 5-fluorouracil (400 mg/m(2)). RESULTS: Of the 92 patients accrued to the study, toxicity data are available for 87 patients and efficacy data for 81 patients. At a median follow-up of 37.5 months, median overall survival is 26.3 months, median progression free survival is 10.7 months and 1-year survival is 85%. The overall response rate is 49.4% (6.2% complete responses). A reduction in the starting doses of irinotecan and 5-fluorouracil decreased the occurrence of vomiting, diarrhea and neutropenia related complications. Bleeding occurred in 37 patients; all events but two were grade 1 or grade 2. There were nine reports of grade 3 or grade 4 thrombo-embolic events. Hypertension of any grade occurred in 13% of patients and proteinuria was infrequent. CONCLUSION: High-dose bevacizumab added to IFL is a well-tolerated and highly active regimen in patients with previously untreated metastatic colorectal cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Terapia Neoadjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Metástase Neoplásica/tratamento farmacológico , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do TratamentoRESUMO
The ethical treatment of cancer patients participating in clinical trials requires that patients are well-informed about the potential benefits and risks associated with participation. When patients enrolled in phase I clinical trials report that their chance of benefit is very high, this is often taken as evidence of a failure of the informed consent process. We argue, however, that some simple themes from the philosophy of language may make such a conclusion less certain. First, the patient may receive conflicting statements from multiple speakers about the expected outcome of the trial. Patients may be reporting the message they like best. Second, there is a potential problem of multivocality. Expressions of uncertainty of the frequency type (e.g., "On average, 5 out of every 100 patients will benefit") can be confused with expressions of uncertainty of the belief type (e.g., "The chance that I will benefit is about 80%"). Patients may be informed using frequency-type statements and respond using belief-type statements. Third, each speech episode involving the investigator and the patient regarding outcomes may subserve multiple speech acts, some of which may be indirect. For example, a patient reporting a high expected benefit may be reporting a belief about the future, reassuring family members, and/or attempting to improve his or her outcome by a public assertion of optimism. These sources of linguistic confusion should be considered in judging whether the patient's reported expectation is grounds for a bioethical concern that there has been a failure in the informed consent process.
Assuntos
Ensaios Clínicos Fase I como Assunto/ética , Compreensão , Consentimento Livre e Esclarecido/ética , Pacientes/psicologia , Relações Médico-Paciente/ética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/psicologia , Feminino , Humanos , Linguística , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/psicologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Medição de Risco , Resultado do Tratamento , IncertezaRESUMO
The Her2/neu (c-erbB-2) oncogene encodes a 185-kDa protein tyrosine kinase which is overexpressed in 20% of breast adenocarcinomas and is recognized by a humanized anti-Her2/neu monoclonal antibody (mAb) (rhu4D5 or Herceptin). Natural killer (NK) cells are capable of mediating antibody-dependent cell cytotoxicity (ADCC) against antibody-coated targets via their expression of a low-affinity receptor for IgG (FcgammaRIII or CD16). NK cells can be expanded in cancer patients via the administration of low-dose interleukin-2 (IL-2) and become potent cytotoxic effectors following exposure to high doses of IL-2. We tested IL-2-activated NK cells against Her2/neu+ (MCF-7Her2/neu) and Her2/neu- (MDA-468) breast cancer cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence or absence of rhu4D5 mAb (effector : target ratio = 10 : 1). Specific lysis of rhu4D5-coated MCF-7Her2/neu and MDA-468 target cells by IL-2-activated NK cells was 35% and 3%, respectively (p < 0.05). Lysis was less than 5% when targets were treated with either the non-humanized mu4D5 mAb or control huIgG. Lysis of rhu4D5-coated MCF-7Her2/neu cells was inhibited by 80 % when NK cells were pre-treated with an anti-Fc receptor antibody prior to use in the cytotoxicity assay. Enhanced ADCC of MCF-7Her2/neu target cells was seen when the effector cells consisted of mononuclear cells obtained from a patient demonstrating significant expansion of NK cells secondary to therapy with low-dose IL-2. Serum from patients receiving infusions of rhu4D5 mAb could substitute for exogenous antibody in the ADCC assay. NK cells activated by rhu4D5-coated tumor cells in the presence of IL-2 also produced large amounts of IFN-gamma with concomitant up-regulation of cell-surface activation markers CD25 and CD69. These results lend support to the concurrent use of rhu4D5 mAb and IL-2 therapy in patients with cancers that express the Her2/neu oncogene.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/terapia , Interleucina-2/farmacologia , Células Matadoras Naturais/imunologia , Animais , Anticorpos Monoclonais Humanizados , Citotoxicidade Celular Dependente de Anticorpos , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Antígeno CD56/análise , Citocinas/biossíntese , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária , Camundongos , Receptor ErbB-2/análise , Receptores de IgG/fisiologia , Trastuzumab , Células Tumorais CultivadasAssuntos
Neoplasias Gastrointestinais/radioterapia , Comitê de Profissionais/organização & administração , Radioterapia (Especialidade)/organização & administração , Projetos de Pesquisa , Antimetabólitos Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Fluoruracila/uso terapêutico , Previsões , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Objetivos OrganizacionaisRESUMO
PURPOSE: To review and assign attribution for the causes of early deaths on two National Cancer Institute-sponsored cooperative group studies involving irinotecan and bolus fluorouracil (5-FU) and leucovorin (IFL). PATIENTS AND METHODS: The inpatient, outpatient, and research records of patients treated on Cancer and Leukemia Group B protocol C89803 and on North Center Cancer Treatment Group protocol N9741 were reviewed by a panel of five medical oncologists not directly involved with either study. Each death was categorized as treatment-induced, treatment-exacerbated, or treatment-unrelated. RESULTS: The records of 44 patients who experienced early deaths on C89803 (21 patients) or N9741 (23 patients) were reviewed. Patients treated with irinotecan plus bolus 5-FU/leucovorin had a three-fold higher rate of treatment-induced or treatment-exacerbated death than patients treated on the other arm(s) of the respective studies. For C89803, these rates were 2.5% (16 of 635) for IFL versus 0.8% (five of 628) for bolus weekly 5-FU and leucovorin. For N9741, these rates were 3.5% (10 of 289) for IFL, 1.1% (three of 277) for oxaliplatin plus bolus and infusional 5-FU and leucovorin, and 1.1% (three of 275) for oxaliplatin plus irinotecan. Multiple gastrointestinal toxicities that often occurred together were characterized into a gastrointestinal syndrome. Sudden, unexpected thromboembolic events were characterized as a vascular syndrome. The majority of deaths in both studies were attributable to one or both of these syndromes. CONCLUSION: Close clinical monitoring, early recognition of toxicities and toxicity syndromes, aggressive therapeutic intervention, and withholding therapy in the presence of unresolved drug-related toxicities is recommended for patients receiving IFL or other intensive chemotherapy regimens.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Causas de Morte , Fluoruracila/administração & dosagem , Gastroenteropatias/induzido quimicamente , Guias como Assunto , Irinotecano , Leucovorina/administração & dosagem , Mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Síndrome , Fatores de Tempo , Doenças Vasculares/induzido quimicamenteRESUMO
PURPOSE/OBJECTIVES: To identify nurses' attitudes and beliefs toward cancer clinical trials and their perceptions about factors influencing patients' participation in these trials. DESIGN: Descriptive. SETTING: National Cancer Institute-designated comprehensive cancer center. SAMPLE: 417 nurses employed at the cancer center were surveyed; 250 (60%) subjects responded. METHODS: 59-item questionnaire. MAIN RESEARCH VARIABLES: Nurses' attitudes toward clinical trials and perceptions of patient understanding of and influences on participation in clinical trials. FINDINGS: 96% of nurses reported that participation in clinical trials is important to improving standards of care; only 56% believed that patients should be encouraged to participate in trials if they had cancer. In multiple regression analyses, older age and being a research nurse were significant predictors of positive attitudes toward clinical trials. Work setting also was a significant predictor of nurses' perceptions of patients' understanding of treatment. Overall, nurses reported that an investigational therapy should have at least a 50% chance of success prior to being offered to patients. CONCLUSIONS: Nurses generally reported that clinical trials are important to improve standards of care; however, attitudes concerning patient participation in clinical trials and perceptions of patient understanding differed by work setting. Nurses have high expectations regarding the benefits of investigational therapy. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a critical role in the care of participants in cancer clinical trials. Targeted interventions that involve nurses to enhance appropriate patient accrual, patient understanding, and patient decision making should result in improved patient care in centers conducting clinical trials.
Assuntos
Atitude do Pessoal de Saúde , Ensaios Clínicos como Assunto , Recursos Humanos de Enfermagem Hospitalar/psicologia , Seleção de Pacientes , Adulto , Feminino , Humanos , Masculino , Análise Multivariada , New York , Análise de RegressãoRESUMO
Chemopreventive strategies hold substantial promise for reducing the incidence of colorectal cancer, the second leading cause of cancer-related mortality in the United States. This review focuses on recent advances in the identification of molecular targets and novel strategies for chemopreventive intervention. Many clinical trials are now in progress to assess the ability of synthetic agents or nutritional supplements to alter either the number of colorectal adenomas or biomarkers associated with colorectal tumorigenesis. Populations under study include genetically defined high-risk people and those with increased risk based on a personal history of colorectal neoplasia. A recent study showing that celecoxib, a cyclooxygenase-2 inhibitor, can alter the natural history of polyp formation in patients with familial adenomatous polyposis has provided a benchmark for the clinical development of other chemopreventive agents and heightened awareness that colorectal cancer is a preventable disease.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias Colorretais/prevenção & controle , Quimioprevenção , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Dietoterapia , Humanos , Vitaminas/uso terapêuticoRESUMO
Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells. ALVAC-CEA B7.1 is a canarypox virus encoding the gene for the tumor-associated antigen carcinoembryonic antigen (CEA) and for a T-cell costimulatory molecule, B7.1. After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells. Patients were vaccinated with vaccine intradermally every other week for 8 weeks. GM-CSF was given s.c. for 5 days beginning 2 days before vaccination. Patients with stable or responding disease after four immunizations received monthly boost injections alone or with GM-CSF. Biopsies of vaccine sites were obtained 48 h after vaccination to evaluate leukocytic infiltration and CEA expression. Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma. Therapy was well tolerated. All of the patients had evidence of leukocytic infiltration and CEA expression in vaccine biopsy sites. In the patients receiving GM-CSF, leukocytic infiltrates were greater in cell number but were less likely to have a predominant lymphocytic infiltrate compared with patients receiving vaccine in the absence of the cytokine adjuvant. After four vaccinations, CEA-specific T-cell precursors were statistically increased in HLA-A2 positive patients who received vaccine alone. However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results. The number of prior chemotherapy regimens was negatively correlated with the generation of a T-cell response, whereas there was a positive correlation between the number of months from the last chemotherapy regimen and the T-cell response. ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.
Assuntos
Vacinas Anticâncer/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neoplasias/tratamento farmacológico , Vacinas Sintéticas/uso terapêutico , Adulto , Idoso , Biópsia , Vacinas Anticâncer/efeitos adversos , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Imunidade/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do Tratamento , Vacinas Sintéticas/efeitos adversosRESUMO
We examined the effect of preoperative chemoradiotherapy on the ability to obtain pathologically negative resection margins in patients undergoing pancreaticoduodenectomy for adenocarcinoma of the head of the pancreas. Between 1987 and 2000, 100 patients underwent Whipple resection with curative intent for primary adenocarcinoma of the head of the pancreas. Pathologic assessment of six margins (proximal and distal superior mesenteric artery, proximal and distal superior mesenteric vein, pancreas, retroperitoneum, common bile duct, and hepatic artery) was undertaken by either frozen section (pancreas and common duct) or permanent section. A margin was considered positive if tumor was present less than 1 mm from the inked specimen. Margins noted to be positive on frozen section were resected whenever possible. Of the 100 patients treated, 47 (47%) underwent postoperative radiation and chemotherapy (group I) and 53 (53%) received preoperative chemoradiotherapy (group II) with either 5-fluorouracil (32 patients) or gemcitabine (21 patients). Patient demographics and operative parameters were similar in the two groups, with the exception of preoperative tumor size (CT scan), which was greater in group II (P < 0.001), and number of previous operations, which was greater in group II (P < 0.0001). Statistical analysis of the number of negative surgical margins clear of tumor was performed using Fisher's exact test. All patients (100%) had six margins assessed for microscopic involvement with tumor. In the preoperative therapy group, 5 (7.5%) of 53 patients had more than one positive margin, whereas 21 (44.7%) of 47 patients without preoperative therapy had more than one margin with disease extension (P < 0.001). Additionally, only 11 (25.6%) of the 47 patients without preoperative therapy had six negative margins vs. 27 (50.9%) of 53 in the group receiving preoperative therapy (P = 0.013). Survival analysis reveals a significant increase in survival in margin-negative patients (P = 0.02). Similarly, a strong trend toward improved disease-free and overall survival is seen in patients with a single positive margin vs. multiple margins. Overall, we find a negative impact on survival with an increasing number of positive margins (P = 0.025, hazard ratio 1.3). When stratified for individual margin status, survival was decreased in patients with positive superior mesenteric artery (P = 0.06) and vein (P = 0.04) margins. However, this has not yet resulted in a significant increase in disease-free or overall survival for patients receiving preoperative therapy (P = 0.07).
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pancreaticoduodenectomia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , GencitabinaRESUMO
BACKGROUND: The oral administration of 5-fluorouracil (5-FU) is hindered by erratic bioavailability due to catabolism of 5-FU by the enzyme dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Eniluracil is a potent inactivator of DPD which results in 100% oral bioavailability of 5-FU. Leucovorin (LV) is another biochemical modulator of 5-FU that potentiates inhibition of thymidylate synthase, the primary target of 5-FU. The goal of this study was to determine the antitumor activity and toxicity of an oral regimen containing eniluracil, 5-FU, and LV in patients with colorectal carcinoma. METHODS: Sixty eligible patients who had previously untreated, measurable, metastatic colorectal carcinoma were treated with oral eniluracil 50 mg on Days 1-7, 5-FU 20 mg/m(2) on Days 2-6, and LV 50 mg on Days 2-6. Cycles were repeated at 28-day intervals. RESULTS: The overall response rate was 13% (95% confidence interval [CI] = 6, 25%), with 1 complete response and 7 partial responses. Three additional patients had partial responses that were not confirmed at subsequent evaluations. The median time to progression of disease was 4.4 months (95% CI = 3.45, 7.69) and the median survival time was 12.6 months (95% CI = 9.1, 14.75). Grade 3-5 toxicity (1 toxic death) occurred in 51 patients (85%). Grade 4 neutropenia occurred in 25 patients (42%), and 18 patients (30%) had Grade 3-4 diarrhea. Twenty-one patients (35%) were hospitalized for toxicity, and 12 (20%) had febrile neutropenia. Baseline creatinine clearance was associated inversely with severe toxicity (P = 0.001). CONCLUSIONS: Although antitumor activity was observed, the frequent occurrence of severe toxicity with this regimen limited its clinical utility. Alternate schedules with a more favorable therapeutic index are undergoing clinical testing and should be pursued. The high level of toxicity observed with orally administered low dose 5-FU underscored the potency of eniluracil as a biochemical modulator.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Uracila/análogos & derivados , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/mortalidade , Carcinoma/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Di-Hidrouracila Desidrogenase (NAD+) , Progressão da Doença , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxirredutases/antagonistas & inibidores , Timidilato Sintase/antagonistas & inibidores , Uracila/administração & dosagem , Uracila/efeitos adversos , Uracila/farmacologiaRESUMO
We conducted a retrospective review of all patients who underwent surgical extirpation for stage III, stage IV, or recurrent carcinoma of the gallbladder. Between 1991 and 1999 ten patients underwent surgical resection for advanced gallbladder cancer. All patients received adjuvant therapy either pre- or postoperatively. Radiotherapy was used in all patients and chemotherapy in 90 per cent of patients. Two patients subsequently underwent resection for locally recurrent disease. An additional patient with stage II disease initially was also treated surgically for a local recurrence. Surgical management involved cholecystectomy and resection of various amounts of liver surrounding the gallbladder bed and regional lymphadenectomy. Contiguously involved structures were resected en bloc. Resection of recurrent disease included excision of all gross tumor. The median overall survival excluding the one 30-day mortality was 53.6 months (range 8-73 months). Four patients have survived 4 or more years, and currently four patients are alive and disease free at 73, 49, 33, and 8 months. Median disease-free interval after each resection of recurrent disease was 13.8 months (range 4-28 months). We conclude that trimodality therapy in selected patients with stage III, IV, or recurrent carcinoma of the gallbladder is possible and may result in prolonged survival.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Colecistectomia , Neoplasias da Vesícula Biliar/terapia , Recidiva Local de Neoplasia/terapia , Doença Aguda , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Quimioterapia Adjuvante , Colecistite/etiologia , Doença Crônica , Feminino , Neoplasias da Vesícula Biliar/complicações , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Icterícia/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Few measures exist to assess physicians' practice style, and there are few data on physicians' practice styles and patterns of care. OBJECTIVES: To use clinical vignettes to measure surgeons' "propensity" for local treatments for early-stage breast cancer and to describe factors associated with propensity. RESEARCH DESIGN AND SUBJECTS: A cross-sectional mailed survey with telephone follow-up of a random sample of 1,000 surgeons treating Medicare beneficiaries in fee-for-service settings. MEASURES: Outcome measures include treatment propensity, self-reported practice, and actual treatment received by the surgeons' patients. RESULTS: Propensities were significantly associated with actual treatment, controlling for covariates. Area Medicare fees were the strongest predictor of propensity, followed by region, attitudes, volume, and gender. For instance, after other factors were considered, surgeons practicing in areas with the highest breast-conserving surgery (BCS) fees were 8.61 (95% CI 2.26-32.73) times more likely to have a BCS propensity than surgeons in areas with the lowest fees. Surgeons with the strongest beliefs in patient participation in treatment decisions were nearly 6 times (95% CI 1.67-20.84) more likely to have a BCS propensity than surgeons with the lowest such beliefs, controlling for covariates. Male surgeons were also independently more likely to have a mastectomy propensity than female surgeons. CONCLUSIONS: Surgeons' propensities explain some of the observed variations in breast cancer treatment patterns among older women. Standardized scenarios provide a practical method to measure practice style and could be used to evaluate physician contributions to shared decision making, practice patterns, costs and outcomes, and adherence to guidelines.