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1.
Prev Chronic Dis ; 18: E71, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264811

RESUMO

We investigated the association between the 5As (Ask, Advise, Assess, Assist, and Arrange) clinical protocol and stage of change among African American smokers who are eligible for low-dose computed tomography screening. In 2019, 60 African American daily smokers aged 55 years or older were recruited in a large hospital in New Orleans, Louisiana. Smokers who received assistance for smoking cessation were more likely to be in the preparation stage than those who did not receive any assistance. Assistance from health professionals is an essential form of support and may substantially enhance smokers' motivation to quit smoking in this population that is at higher risk for mortality from lung cancer.


Assuntos
Negro ou Afro-Americano/psicologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/etnologia , Fumantes/psicologia , Abandono do Hábito de Fumar/etnologia , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Fumantes/estatística & dados numéricos , Fumar , Abandono do Hábito de Fumar/psicologia
2.
Cancer ; 120(22): 3575-83, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25043153

RESUMO

BACKGROUND: Despite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC). METHODS: Participants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2-4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2-6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test. RESULTS: Four hundred thirty patients were enrolled in this study. Forty-seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects. CONCLUSIONS: In this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients.


Assuntos
Aminas/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Vômito/prevenção & controle , Ácido gama-Aminobutírico/uso terapêutico , Adulto , Idoso , Aminas/administração & dosagem , Aminas/efeitos adversos , Ácidos Cicloexanocarboxílicos/administração & dosagem , Ácidos Cicloexanocarboxílicos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Satisfação do Paciente , Fatores de Tempo , Vômito/induzido quimicamente , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/efeitos adversos
3.
Artigo em Inglês | MEDLINE | ID: mdl-35329141

RESUMO

BACKGROUND: Lung cancer patients have the worst outcomes when affected by coronavirus disease 2019 (COVID-19). The molecular mechanisms underlying the association between lung cancer and COVID-19 remain unknown. The objective of this investigation was to determine whether there is crosstalk in molecular perturbation between COVID-19 and lung cancer, and to identify a molecular signature, molecular networks and signaling pathways shared by the two diseases. METHODS: We analyzed publicly available gene expression data from 52 severely affected COVID-19 human lung samples, 594 lung tumor samples and 54 normal disease-free lung samples. We performed network and pathways analysis to identify molecular networks and signaling pathways shared by the two diseases. RESULTS: The investigation revealed a signature of genes associated with both diseases and signatures of genes uniquely associated with each disease, confirming crosstalk in molecular perturbation between COVID-19 and lung cancer. In addition, the analysis revealed molecular networks and signaling pathways associated with both diseases. CONCLUSIONS: The investigation revealed crosstalk in molecular perturbation between COVID-19 and lung cancer, and molecular networks and signaling pathways associated with the two diseases. Further research on a population impacted by both diseases is recommended to elucidate molecular drivers of the association between the two diseases.


Assuntos
COVID-19 , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Transdução de Sinais
4.
Am Heart J Plus ; 13: 100112, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35252907

RESUMO

SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-diagnosed adults with hypertension, we assessed associations between antihypertensive exposure (ACEI/ARB vs. non-ACEI/ARB antihypertensives, as well as between ACEI- vs. ARB) at the time of COVID-19 diagnosis, using electronic health record data from PCORnet health systems. The primary outcomes were all-cause hospitalization or death (outpatient cohort) or all-cause death (inpatient), analyzed via Cox regression weighted by inverse probability of treatment weights. From February 2020 through December 9, 2020, 11,246 patients (3477 person-years) and 2200 patients (777 person-years) were included from 17 health systems in outpatient and inpatient cohorts, respectively. There were 1015 all-cause hospitalization or deaths in the outpatient cohort (incidence, 29.2 events per 100 person-years), with no significant difference by ACEI/ARB use (adjusted HR 1.01; 95% CI 0.88, 1.15). In the inpatient cohort, there were 218 all-cause deaths (incidence, 28.1 per 100 person-years) and ACEI/ARB exposure was associated with reduced death (adjusted HR, 0.76; 95% CI, 0.57, 0.99). ACEI, versus ARB exposure, was associated with higher risk of hospitalization in the outpatient cohort, but no difference in all-cause death in either cohort. There was no evidence of effect modification across pre-specified baseline characteristics. Our results suggest ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19.

5.
Contemp Clin Trials ; 119: 106813, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35660539

RESUMO

RATIONALE AND OBJECTIVE: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. STUDY DESIGN: Multicenter, pragmatic, randomized controlled clinical trial. SETTING AND PARTICIPANTS: 6650 individuals with African ancestry and hypertension from 13 health systems. INTERVENTION: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OUTCOMES: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. RESULTS: To date, the trial has enrolled 3423 participants. CONCLUSIONS: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.govNCT04191824.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Negro ou Afro-Americano , Anti-Hipertensivos , Apolipoproteína L1 , Pressão Sanguínea , Testes Genéticos , Humanos , Farmacogenética
6.
Adv Ther ; 38(1): 782-791, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33108622

RESUMO

INTRODUCTION: The COVID-19 global pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia and subsequent respiratory failure threaten to overrun hospital critical care units globally. New agents that address the hyperinflammatory "cytokine storm" and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively. Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, with the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding compared to commercially available heparin. METHODS: This study is a randomized, double-blind, placebo-controlled, phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care in hospitalized adults with COVID-19 who require supplemental oxygen. Phase 2 will enroll 12 participants in each of two dose-escalating cohorts to confirm the safety of DSTAT in this population. Following review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, phase 3 will enroll approximately 450 participants randomized to DSTAT or placebo. The primary endpoint is the proportion of participants who survive and do not require mechanical ventilation through day 28. DISCUSSION: Advances in standard of care, recent emergency use authorizations, and positive data with dexamethasone have likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement in the NIAID score will be essential to provide a measure of drug effect on recovery. Analysis of additional endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble-RAGE, D-dimer), will be performed to further define the effect of DSTAT in patients with COVID-19 infection. TRIAL REGISTRATION: ClinicalTrials.gov identifier; NCT04389840, Registered 13 May 2020.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/complicações , Heparina/uso terapêutico , Insuficiência Respiratória/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/etiologia , SARS-CoV-2/efeitos dos fármacos , Resultado do Tratamento
7.
J Pain Symptom Manage ; 62(5): 987-996, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33864847

RESUMO

CONTEXT: Early integrated palliative care improves quality of life, but palliative care programs are underutilized. Psychoeducational interventions explaining palliative care may increase patients' readiness for palliative care. OBJECTIVES: To 1) collaborate with stakeholders to develop the EMPOWER 2 intervention explaining palliative care, 2) examine acceptability, 3) evaluate feasibility and preliminary efficacy. METHODS: The research was conducted at a North American cancer center and involved 21 stakeholders and 10 patient-participants. Investigators and stakeholders iteratively developed the intervention. Stakeholders rated acceptability of the final intervention. Investigators implemented a pre-post trial to examine the feasibility of recruiting 10 patients with metastatic cancer within one month and with a ≥50% consent rate. Preliminary efficacy outcomes were changes in palliative care knowledge and attitudes. RESULTS: Using feedback from four stakeholder meetings, we developed a multimedia intervention tailored to three levels of health-literacy. The intervention provides knowledge and reassurance about the purpose and nature of palliative care, addressing cognitive and emotional barriers to utilization. Stakeholders rated the intervention and design process highly acceptable (3.78/4.00). The pilot met a priori feasibility criteria (10 patients enrolled in 14 days; 83.3% consent rate). The intervention increased palliative care knowledge by 83.1% and improved attitudes by 18.9 points on a 0 to 51 scale (Ps < 0.00001). CONCLUSIONS: This formative research outlines the development of a psychoeducational intervention about palliative care. The intervention is acceptable, feasible, and demonstrated promising pilot test results. This study will guide clinical teams in improving patients' readiness for palliative care and inform the forthcoming EMPOWER 3 randomized clinical trial.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Emoções , Humanos , Cuidados Paliativos , Qualidade de Vida
8.
Support Care Cancer ; 18(3): 321-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19468757

RESUMO

PURPOSE: The purpose of this study is to test the ability of risedronate and estradiol, alone or in combination, to prevent bone loss associated with androgen deprivation therapy in men with prostate cancer. MATERIALS AND METHODS: This is a randomized placebo-controlled trial of risedronate and estradiol, alone or in combination, in men with prostate cancer receiving androgen deprivation therapy. The primary outcome was change in hip bone mineral density at 1 year. RESULTS: No statistical difference was found among the groups for bone mineral density changes. The only side effects of note were increased gynecomastia and breast tenderness associated with estrogen therapy. The study was limited by poor accrual and subsequent lack of statistical power. CONCLUSIONS: Men receiving androgen deprivation therapy for prostate cancer are at risk for bone loss and should receive appropriate bone density monitoring and preventive advice about calcium, vitamin D, exercise, and fall prevention. Prescription drugs proven in this patient population should be used when the risk of fracture is high.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Estradiol/uso terapêutico , Ácido Etidrônico/análogos & derivados , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Neoplasias da Próstata/tratamento farmacológico , Idoso , Método Duplo-Cego , Ácido Etidrônico/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Ginecomastia/induzido quimicamente , Humanos , Masculino , Ácido Risedrônico
9.
Breast Cancer Res ; 11(5): R73, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19811637

RESUMO

INTRODUCTION: MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. METHODS: Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. RESULTS: Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours. CONCLUSIONS: Repeated iv administration of AS1402 was well tolerated, with a maximum tolerated dose (MTD) exceeding 16 mg/kg, the highest dose administered in this study. The half-life and exposure of AS1402 were such that weekly dosing could achieve plasma concentrations corresponding to the maximal ADCC activity observed in vitro. A phase II study is ongoing to evaluate the clinical activity of AS1402 in patients with advanced breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00096057.


Assuntos
Anticorpos Monoclonais/farmacocinética , Neoplasias da Mama/terapia , Mucina-1/imunologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Citotoxicidade Celular Dependente de Anticorpos , Neoplasias da Mama/enzimologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Estudos de Coortes , Relação Dose-Resposta Imunológica , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/biossíntese
10.
Clin Pharmacokinet ; 48(3): 199-209, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19385713

RESUMO

BACKGROUND AND OBJECTIVE: Bortezomib, an antineoplastic for the treatment of relapsed multiple myeloma and mantle cell lymphoma, undergoes metabolism through oxidative deboronation by cytochrome P450 (CYP) enzymes, primarily CYP3A4 and CYP2C19. Omeprazole, a proton-pump inhibitor, is primarily metabolized by and demonstrates high affinity for CYP2C19. This study investigated whether coadministration of omeprazole affected the pharmacokinetics, pharmacodynamics and safety profile of bortezomib in patients with advanced cancer. The variability of bortezomib pharmacokinetics with CYP enzyme polymorphism was also investigated. PATIENTS AND METHODS: This open-label, crossover, pharmacokinetic drug-drug interaction study was conducted at seven institutions in the US and Europe between January 2005 and August 2006. Patients who had advanced solid tumours, non-Hodgkin's lymphoma or multiple myeloma, were aged >/=18 years, weighed >/=50 kg and had a life expectancy of >/=3 months were eligible. Patients received bortezomib 1.3 mg/m2 on days 1, 4, 8 and 11 for two 21-day cycles, plus omeprazole 40 mg in the morning of days 6-10 and in the evening of day 8 in either cycle 1 (sequence 1) or cycle 2 (sequence 2). On day 21 of cycle 2, patients benefiting from therapy could continue to receive bortezomib for six additional cycles. Blood samples for pharmacokinetic/pharmacodynamic evaluation were collected prior to and at various timepoints after bortezomib administration on day 8 of cycles 1 and 2. Blood samples for pharmacogenomics were also collected. Pharmacokinetic parameters were calculated by noncompartmental analysis of plasma concentration-time data for bortezomib administration on day 8 of cycles 1 and 2, using WinNonlin version 4.0.1.a software. The pharmacodynamic profile was assessed using a whole-blood 20S proteasome inhibition assay. RESULTS: Twenty-seven patients (median age 64 years) were enrolled, 12 in sequence 1 and 15 in sequence 2, including eight and nine pharmacokinetic-evaluable patients, respectively. Bortezomib pharmacokinetic parameters were similar when bortezomib was administered alone or with omeprazole (maximum plasma concentration 120 vs 123 ng/mL; area under the plasma concentration-time curve from 0 to 72 hours 129 vs 135 ng . h/mL). The pharmacodynamic parameters were also similar (maximum effect 85.8% vs 93.7%; area under the percent inhibition-time curve over 72 hours 4052 vs 3910 % x h); the differences were not statistically significant. Pharmacogenomic analysis revealed no meaningful relationships between CYP enzyme polymorphisms and pharmacokinetic/pharmacodynamic parameters. Toxicities were generally similar between patients in sequence 1 and sequence 2, and between cycle 1 and cycle 2 in both treatment sequences. Among 26 evaluable patients, 13 (50%) were assessed as benefiting from bortezomib at the end of cycle 2 and continued to receive treatment. CONCLUSION: No impact on the pharmacokinetics, pharmacodynamics and safety profile of bortezomib was seen with coadministration of omeprazole. Concomitant administration of bortezomib and omeprazole is unlikely to cause clinically significant drug-drug interactions and is unlikely to have an impact on the efficacy or safety of bortezomib.


Assuntos
Antiulcerosos/farmacocinética , Antineoplásicos/farmacocinética , Hidrocarboneto de Aril Hidroxilases/antagonistas & inibidores , Ácidos Borônicos/farmacocinética , Neoplasias/metabolismo , Omeprazol/farmacocinética , Pirazinas/farmacocinética , Idoso , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Área Sob a Curva , Ácidos Borônicos/farmacologia , Ácidos Borônicos/uso terapêutico , Bortezomib , Estudos Cross-Over , Citocromo P-450 CYP2C19 , Esquema de Medicação , Interações Medicamentosas , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Neoplasias/tratamento farmacológico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/farmacocinética , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Pirazinas/farmacologia , Pirazinas/uso terapêutico
11.
Transl Cancer Res ; 8(Suppl 4): S431-S442, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35117119

RESUMO

BACKGROUND: The purpose of this study is to investigate knowledge, attitudes, and smoking cessation needs for African Americans who receive low dose computed tomography (LDCT) in an effort to reduce the health burden of lung cancer. METHODS: A mixed method study was conducted among African Americans who received LDCT. Data were gathered using a self-administered questionnaire and structured in-depth interview. Descriptive statistics were used to provide summary information on knowledge, attitude and smoking behaviors. Thematic analysis was used to analyze interview data. The sample size for both the quantitative and qualitative approach was fifteen. RESULTS: The results showed that 73% of participants were male, the mean age was 61.8 (SD =4.6) years old, and 66.7% of participants had an income less than $20,000. Eighty percent had an education level of high school or below and 73.3% were overweight or obese. Smoking history was long (mean years =39 SD =14.9), but the number of cigarettes smoked per day was low (mean =9.2 SD =7.3), and 64% of the patients had a low nicotine dependence. Assessment of knowledge and attitudes towards LDCT revealed that participants had a moderate/lower knowledge score (mean =4.3 SD =2.6), and most had a positive attitude. All participants planned to quit smoking, with 73% planning to quit within the next 6 months. Similar findings were also observed in the qualitative analysis. CONCLUSIONS: African Americans who receive LDCT lung cancer screening in this study have a moderate/lower knowledge score and positive attitude towards LDCT. Most were not heavy smokers and had a lower nicotine dependence. Understanding the factors associated with smoking cessation among at-risk African American smokers will help reduce disparities in lung cancer burden, and is important to improve health for medically underserved minority populations.

12.
World J Gastrointest Oncol ; 8(1): 99-104, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26798440

RESUMO

Over the past couple of decades considerable progress has been made in the management of metastatic colorectal cancers (mCRC) leading to a significant improvement in five-year survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of cancer and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article we will discuss various targeted therapies in the management of mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well.

13.
Ochsner J ; 15(2): 187-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26130984

RESUMO

BACKGROUND: Rituximab has rarely been associated with acute coronary syndrome (ACS). We report the case of a patient in whom rituximab, a monoclonal antibody used to treat lymphomas of B-cell origin, induced ST elevation myocardial infarction. CASE REPORT: A 46-year-old male patient diagnosed with stage II non-Hodgkin lymphoma presented to the emergency department with acute crushing, substernal chest pain that radiated to his back 1 day after a chemotherapy infusion with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. An electrocardiogram revealed normal sinus rhythm with ST elevations in the inferior leads. The patient underwent primary percutaneous coronary intervention (PCI) of his right coronary artery and first diagonal artery with placement of drug-eluting stents. He did well postprocedure and resumed therapy with rituximab under close monitoring by the cardiology and oncology departments without any further cardiac events. CONCLUSION: In patients with ACS because of chemotherapy, complete revascularization during PCI should be considered.

14.
Onco Targets Ther ; 5: 133-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22930641

RESUMO

The biological agents approved for the treatment of patients with metastatic colorectal cancer - bevacizumab, a monoclonal antibody that targets vascular endothelial growth factor A, along with cetuximab and panitumumab, two monoclonal antibodies that target the epidermal growth factor receptor - are associated with a number of adverse events that range in severity from relatively mild to potentially life threatening. Hypertension, thromboembolic events, proteinuria, bleeding, and gastrointestinal perforation have all been associated with bevacizumab, while dermatologic toxicities are common with cetuximab and panitumumab. Hypersensitivity reactions and hypomagnesemia are also a concern with cetuximab and panitumumab. The frequency of these adverse events in randomized clinical trials is reviewed, and recommendations for managing these events in patients undergoing treatment for metastatic colorectal cancer are provided.

15.
Clin Colorectal Cancer ; 11(1): 31-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21729678

RESUMO

BACKGROUND: Patients with multiple liver metastases from colorectal cancer are at high risk of recurrence after resection. Hepatic artery infusion (HAI) alternating with systemic therapy after surgical resection may improve survival after surgery. METHODS: Patients with liver-only metastases from colorectal cancer amenable to resection/cryoablation were eligible. Previous adjuvant chemotherapy for a completely resected primary tumor was allowed. Alternating courses of HAI and systemic therapy included floxuridine (FUDR) by HAI. Systemic chemotherapy consisted of bolus leucovorin (LV) plus 5-fluorouracil (5-FU). RESULTS: Forty-nine patients had complete resection of their liver metastases, with 44% having more than 4 hepatic metastases and 78% having bilobar disease. Thirty-six patients had HAI FUDR alternating with systemic therapy. Patients received a median of 3.5 cycles (range, 1-4) and 3 cycles (range, 0-6) of therapy with HAI FUDR and systemic therapy, respectively. At the time of final analysis the estimated median disease-free survival and hepatic disease-free survival was 1.2 years (95% confidence interval [CI], 0.9-2.1) and 1.8 years (95% CI, 1.8-not available), respectively. Eleven patients (31%) were alive at this writing. All surviving patients had a minimum of 5.5 years of follow-up. CONCLUSION: This trial of adjuvant chemotherapy in patients who underwent complete resection with unfavorable characteristics demonstrates apparent improvement in outcome compared with historical series treated with surgery alone. However the results of this trial and other randomized trials of HAI do not appear to support its use at this time because of the development of more effective systemic options.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/terapia , Artéria Hepática/cirurgia , Neoplasias Hepáticas/terapia , Metastasectomia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Criocirurgia , Feminino , Floxuridina/administração & dosagem , Fluoruracila/administração & dosagem , Seguimentos , Artéria Hepática/patologia , Humanos , Infusões Intra-Arteriais , Leucovorina/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento
17.
Ochsner J ; 4(3): 163-7, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-22822340

RESUMO

Chemotherapy is effective in the treatment of colon cancer when used both as adjuvant therapy and for metastatic disease. It has also been shown to improve survival. Novel therapies are currently being evaluated in clinical trials. To continue our progress, it is important that clinical trials be offered to patients undergoing treatment for colon cancer.

18.
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