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1.
Cancer ; 130(13): 2384-2394, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38386696

RESUMO

BACKGROUND: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer. METHODS: Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect. RESULTS: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS-RC group reported significantly higher acceptability of the study. CONCLUSIONS: SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.


Assuntos
Sobreviventes de Câncer , Qualidade de Vida , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Pessoa de Meia-Idade , Feminino , Masculino , Projetos Piloto , Idoso , Adulto
2.
N Engl J Med ; 375(2): 134-42, 2016 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-27410922

RESUMO

BACKGROUND: We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS: In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS: In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS: Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Benzodiazepinas/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/efeitos adversos , Aprepitanto , Benzodiazepinas/efeitos adversos , Dexametasona/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Náusea/induzido quimicamente , Olanzapina , Vômito/induzido quimicamente
3.
Cardiooncology ; 9(1): 44, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057847

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICI) and Tyrosine kinase inhibitors (TKI) are effective for several types of cancers, but they can have several cardiotoxicity sides effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that were successfully treated with high-dose steroids and PCI. CASE PRESENTATION: Seventy-two year-old man patient treated with on pembrolizumab 200 mg IV every 3 weeks and Axitinib 5 mg PO q12h for the past 5 months complained of acute shortness of breath, altered mental status, and chronic diarrhea. Coronary angiography demonstrated a thrombotic lesion in the right coronary artery (RCA) that was treated successfully with percutaneous coronary intervention (PCI). Despite PCI he continued to complain of shortness of breath further workup with Cardiac MRI (CMR) was obtained showed an ejection fraction of 38%, small pericardial effusion, and delayed gadolinium enhancement (DGE) in the inferior wall suggestive of myocarditis. An empirical trial of high-dose steroids improved all patient symptoms and ejection fraction; therefore, the chemotherapy regimen was changed. CONCLUSION: This case report highlights the potential vasculogenic effects of Axitinib and immune-related myocarditis of pembrolizumab. Cardiologists and oncologists should be vigilant for the cardiotoxic effects of Axitinib and pembrolizumab.

4.
J Clin Oncol ; 41(2): 186-197, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36166727

RESUMO

PURPOSE: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma, leading to broad regulatory approval. Little prospective data exist to guide the choice of either initial therapy or treatment sequence in this population. This study was conducted to determine which initial treatment or treatment sequence produced the best efficacy. PATIENTS AND METHODS: In a phase III trial, patients with treatment-naive BRAFV600-mutant metastatic melanoma were randomly assigned to receive either combination nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) in step 1, and at disease progression were enrolled in step 2 to receive the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D). The primary end point was 2-year overall survival (OS). Secondary end points were 3-year OS, objective response rate, response duration, progression-free survival, crossover feasibility, and safety. RESULTS: A total of 265 patients were enrolled, with 73 going onto step 2 (27 in arm C and 46 in arm D). The study was stopped early by the independent Data Safety Monitoring Committee because of a clinically significant end point being achieved. The 2-year OS for those starting on arm A was 71.8% (95% CI, 62.5 to 79.1) and arm B 51.5% (95% CI, 41.7 to 60.4; log-rank P = .010). Step 1 progression-free survival favored arm A (P = .054). Objective response rates were arm A: 46.0%; arm B: 43.0%; arm C: 47.8%; and arm D: 29.6%. Median duration of response was not reached for arm A and 12.7 months for arm B (P < .001). Crossover occurred in 52% of patients with documented disease progression. Grade ≥ 3 toxicities occurred with similar frequency between arms, and regimen toxicity profiles were as anticipated. CONCLUSION: Combination nivolumab/ipilimumab followed by BRAF and MEK inhibitor therapy, if necessary, should be the preferred treatment sequence for a large majority of patients.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Ipilimumab , Nivolumabe/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Prospectivos , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Piridonas , Oximas , Progressão da Doença , Quinases de Proteína Quinase Ativadas por Mitógeno , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Mutação
5.
J Clin Oncol ; 39(24): 2647-2655, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33945288

RESUMO

PURPOSE: Combination of antiprogrammed cell death protein-1 (PD-1) plus anti-cytotoxic T-cell lymphocyte-4 (anti-CTLA-4) immunotherapy shows greater response rates (RRs) than anti-PD-1 antibody alone in melanoma, but RR after initial anti-PD-1 and programmed death ligand-1 (PD-L1) antibody progression awaits robust investigation. Anti-CTLA-4 antibody alone after anti-PD-1/L1 antibody progression has a historical RR of 13%. We report the results of the first prospective clinical trial evaluating ipilimumab 1 mg/kg plus pembrolizumab following progression on anti-PD-1 immunotherapy. METHODS: Patients with advanced melanoma who had progressed on anti-PD-1/L1 antibody as immediate prior therapy (including non-anti-CTLA-4 antibody combinations) were eligible. Patients received pembrolizumab 200 mg plus ipilimumab 1 mg/kg once every 3 weeks for four doses, followed by pembrolizumab monotherapy. The primary end point was RR by irRECIST. After 35 patients, the trial met the primary end point and was expanded to enroll a total of 70 patients to better estimate the RR. RESULTS: Prior treatments included 60 on anti-PD-1 antibody alone and 10 on anti-PD-1/L1 antibody-based combinations. Thirteen patients had progressed in the adjuvant setting. The median length of prior treatment with anti-PD-1/L1 antibody was 4.8 months. Response assessments included five complete and 15 partial responses, making the irRECIST RR 29% among the entire trial population. The median progression-free survival was 5.0 months, and the median overall survival was 24.7 months. The median duration of response was 16.6 months. There was no difference in median time on prior anti-PD1/L1 or time to PD1 + CTLA4 initiation between responders and nonresponders. Grade 3-4 drug-related adverse events occurred in 27% of patients. Responses occurred in PD-L1-negative, non-T-cell-inflamed, and intermediate tumor phenotypes. CONCLUSION: To our knowledge, this is the first prospective study in melanoma of pembrolizumab plus low-dose ipilimumab after anti-PD-1/L1 immunotherapy failure, demonstrating significant antitumor activity and tolerability.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Masculino , Pessoa de Meia-Idade
7.
Oncotarget ; 4(4): 542-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23625538

RESUMO

The prostate-specific antigen (PSA) test has served as a blood marker of prostate cancer (PCa), and for monitoring recurrence/metastasis in patients after therapeutic intervention. However, the applicability/reliability of the PSA test was recently questioned as it is not without challenges, in particular in men who have PCa without an elevated PSA (false negative), or in men who are disease-free with elevated levels of PSA (false positive). Galectin-3 is a tumor-associated protein; present in the seminal fluid and is a substrate for the PSA enzyme e.g., a chymotrypsin-like serine protease. We hypothesized that the cleavage status and level of galectin-3 in the prostate tissue and sera are associated with PCa. Thus, we compared galectin-3 levels obtained from sera of non-cancer urology patients to those of metastatic PCa patients. The data were confirmed by analyzing PCa tissue arrays. Here, we report that galectin-3 levels in the sera of patients with metastatic PCa were uniformly higher as compared to the non-cancer patient controls. The data suggest that galectin-3 serum level may be a useful serum complementary marker to the PSA blood test to be used for initial and follow-up PSA complimentary diagnostic/prognostic tool for recurrence in PCa patients.


Assuntos
Biomarcadores Tumorais/sangue , Detecção Precoce de Câncer/métodos , Galectina 3/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Adulto , Western Blotting , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Imunoprecipitação , Masculino
8.
Artigo em Inglês | MEDLINE | ID: mdl-24451755

RESUMO

Prostate cancer is the most common nonskin malignant neoplasm in men worldwide. In the United States, 241,740 new diagnoses of prostate cancer and 28,170 prostate cancer deaths have been estimated for 2012, representing 28% of new cancer cases and 10% of male cancer deaths.(1) Although metastatic prostate cancer remains an incurable disease, substantial advances have been made in therapeutic options available for men in the past several years. Development of novel agents that modulate the androgen receptor pathway, growth factor signaling pathways, and immune function and bone targeting pathways has been the focus of therapeutic strategies because of its significance in the biology of prostate cancer progression. Several of the agents have gained U.S. Food and Drug Administration (FDA) approval, whereas many are in late-stage clinical trials. With the growth of available treatment options, a major challenge as we move forward will be to determine the best sequence and/or combination of therapy that will result in maximum clinical efficacy with minimum toxicity. Highlighted in this publication are several of the exciting advances in prostate cancer therapy for patients with metastatic, castrate-resistant prostate cancer.

9.
Expert Opin Biol Ther ; 11(11): 1519-24, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21877997

RESUMO

INTRODUCTION: Advanced malignancies that are refractory to standard chemotherapy have few treatment options. Conatumumab is an investigational, fully human monoclonal agonist antibody directed at human death receptor DR5, which is expressed in multiple advanced cancers. AREAS COVERED: The rationale for the use of conatumumab based on in vitro, in vivo, Phase I, and Phase II data will be discussed. EXPERT OPINION: Conatumumab, at a dose of 20 mg/kg every 2 weeks, has demonstrated acceptable safety and tolerability in patients with advanced tumors based on available and published data. Further clinical trials are underway evaluating the use of conatumumab in combination with chemotherapeutic and targeted agents.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/antagonistas & inibidores , Adulto , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/farmacocinética , Humanos , Neoplasias/imunologia , Resultado do Tratamento
10.
J Am Soc Echocardiogr ; 21(1): 90.e1, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17689922

RESUMO

A 61-year-old man presented 9 months after bioprosthetic mitral valve implantation with progressive exertional dyspnea. Transesophageal echocardiography revealed severe mitral stenosis with diffuse leaflet thickening but no calcification. Subsequent pathologic examination of the valve demonstrated infiltrating fibroconnective tissue and chronic inflammation. Careful echocardiographic follow-up of this valve type may be warranted, especially in patients with early recurrent symptoms.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Estenose da Valva Mitral/etiologia , Estenose da Valva Mitral/fisiopatologia , Falha de Prótese , Ecocardiografia Transesofagiana , Seguimentos , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
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