RESUMO
Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapiaRESUMO
Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis; as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapiaRESUMO
Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-non-da-living-guideline.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapiaRESUMO
Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See Appendix 1 (online only) for disclaimers and other important information. Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/terapiaRESUMO
PURPOSE: To provide evidence-based recommendations updating the 2021 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) with driver alterations. METHODS: ASCO updated recommendations on the basis of an ongoing systematic review of randomized control trials from 2020 to 2021. RESULTS: This guideline update reflects changes in evidence since the previous update. Two studies provide the evidence base. Outcomes of interest include efficacy and safety. RECOMMENDATIONS: For patients with an anaplastic lymphoma kinase rearrangement, a performance status (PS) of 0-2, and previously untreated NSCLC, clinicians should offer alectinib or brigatinib or lorlatinib. For patients with an anaplastic lymphoma kinase rearrangement, a PS of 0-2, and previously untreated NSCLC, if alectinib, brigatinib, or lorlatinib are not available, clinicians should offer ceritinib or crizotinib. For patients with a RET rearrangement, a PS of 0-2, and previously untreated NSCLC, clinicians may offer selpercatinib or pralsetinib. In second line, for patients with a RET rearrangement who have not received RET-targeted therapy, clinicians may offer selpercatinib or pralsetinib.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Aminopiridinas , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/uso terapêutico , Humanos , Lactamas , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Compostos Organofosforados , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis , PirimidinasRESUMO
PURPOSE: To provide evidence-based recommendations updating the 2020 ASCO and Ontario Health (Cancer Care Ontario) guideline on systemic therapy for patients with stage IV non-small-cell lung cancer without driver alterations. METHODS: ASCO updated recommendations on the basis of an ongoing systematic review of randomized clinical trials from 2018 to 2021. RESULTS: This guideline update reflects changes in evidence since the previous update. Five randomized clinical trials provide the evidence base. Outcomes of interest include efficacy and safety. RECOMMENDATIONS: In addition to 2020 options for patients with high programmed death ligand-1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%), nonsquamous cell carcinoma (non-SCC), and performance status (PS) 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression (TPS ≥ 50%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilumumab alone or nivolumab and ipilimumab plus chemotherapy. With negative (0%) and low positive PD-L1 expression (TPS 1%-49%), non-SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or nivolumab and ipilimumab plus chemotherapy. With high PD-L1 expression, SCC, and PS 0-1, clinicians may offer single-agent atezolizumab. With high PD-L1 expression, squamous cell carcinoma (SCC), and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With negative and low positive PD-L1 expression, SCC, and PS 0-1, clinicians may offer nivolumab and ipilimumab alone or in combination with two cycles of platinum-based chemotherapy. With non-SCC who received an immune checkpoint inhibitor and chemotherapy as first-line therapy, clinicians may offer second-line paclitaxel plus bevacizumab. With non-SCC, who received chemotherapy with or without bevacizumab and immune checkpoint inhibitor therapy, clinicians should offer the options of third-line single-agent pemetrexed, docetaxel, or paclitaxel plus bevacizumab.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1 , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Docetaxel/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Ipilimumab/uso terapêutico , Neoplasias Pulmonares/patologia , Nivolumabe/uso terapêutico , Paclitaxel/uso terapêutico , Pemetrexede/uso terapêuticoRESUMO
PURPOSE: To update recommendations of the ASCO systemic therapy for hormone receptor (HR)-positive metastatic breast cancer (MBC) guideline. METHODS: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. RESULTS: Fifty-one articles met eligibility criteria and form the evidentiary basis for the recommendations. RECOMMENDATIONS: Alpelisib in combination with endocrine therapy (ET) should be offered to postmenopausal patients, and to male patients, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, ABC, or MBC following prior endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor. Clinicians should use next-generation sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA mutations. If no mutation is found in cell-free DNA, testing in tumor tissue, if available, should be used as this will detect a small number of additional patients with PIK3CA mutations. There are insufficient data at present to recommend routine testing for ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC. For BRCA1 or BRCA2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered in the 1st-line through 3rd-line setting. A nonsteroidal aromatase inhibitor (AI) and a CDK4/6 inhibitor should be offered to postmenopausal women with treatment-naïve HR-positive MBC. Fulvestrant and a CDK4/6 inhibitor should be offered to patients with progressive disease during treatment with AIs (or who develop a recurrence within 1 year of adjuvant AI therapy) with or without one line of prior chemotherapy for metastatic disease, or as first-line therapy. Treatment should be limited to those without prior exposure to CDK4/6 inhibitors in the metastatic setting.Additional information can be found at www.asco.org/breast-cancer-guidelines.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia de Alvo Molecular , PrognósticoRESUMO
PURPOSE: To provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) with driver alterations. A guideline update for systemic therapy for patients with stage IV NSCLC without driver alterations was published separately. METHODS: The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel updated recommendations based on a systematic review of randomized controlled trials (RCTs) from December 2015 to January 2020 and meeting abstracts from ASCO 2020. RESULTS: This guideline update reflects changes in evidence since the previous update. Twenty-seven RCTs, 26 observational studies, and one meta-analysis provide the evidence base (total 54). Outcomes of interest included efficacy and safety. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS: All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations, when possible, following other existing high-quality testing guidelines. Most patients should receive targeted therapy for these alterations: Targeted therapies against ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions should be offered to patients, either as initial or second-line therapy when not given in the first-line setting. New or revised recommendations include the following: Osimertinib is the optimal first-line treatment for patients with activating epidermal growth factor receptor mutations (exon 19 deletion, exon 21 L858R, and exon 20 T790M); alectinib or brigatinib is the optimal first-line treatment for patients with anaplastic lymphoma kinase fusions. For the first time, to our knowledge, the guideline includes recommendations regarding RET, MET, and NTRK alterations. Chemotherapy is still an option at most stages.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicina Baseada em Evidências , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Guias de Prática Clínica como Assunto/normas , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico , Sociedades MédicasRESUMO
PURPOSE: The aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC) without driver alterations. A guideline update for patients with stage IV NSCLC with driver alterations will be published separately. METHODS: The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel made updated recommendations based on a systematic review of randomized controlled trials from December 2015 to 2019. RESULTS: This guideline update reflects changes in evidence since the previous guideline update. Five randomized controlled trials provide the evidence base. Additional literature suggested by the Expert Panel is discussed. RECOMMENDATIONS: Recommendations apply to patients without driver alterations in epidermal growth factor receptor or ALK. For patients with high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non-squamous cell carcinoma (non-SCC), the Expert Panel recommends single-agent pembrolizumab. Additional treatment options include pembrolizumab/carboplatin/pemetrexed, atezolizumab/carboplatin/paclitaxel/bevacizumab, or atezolizumab/carboplatin/nab-paclitaxel. For most patients with non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1, the Expert Panel recommends pembrolizumab/carboplatin/pemetrexed. Additional options are atezolizumab/carboplatin/nab-paclitaxel, atezolizumab/carboplatin/paclitaxel/bevacizumab, platinum-based two-drug combination chemotherapy, or non-platinum-based two-drug therapy. Single-agent pembrolizumab is an option for low positive PD-L1. For patients with high PD-L1 expression (TPS ≥ 50%) and SCC, the Expert Panel recommends single-agent pembrolizumab. An additional treatment option is pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel). For most patients with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%), the Expert Panel recommends pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy. Single-agent pembrolizumab is an option in select cases of low positive PD-L1. Recommendations are conditional on the basis of histology, PD-L1 status, and/or the presence or absence of contraindications. Additional information is available at www.asco.org/lung-cancer-guidelines.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Feminino , Guias como Assunto , Humanos , Masculino , Estadiamento de NeoplasiasRESUMO
PURPOSE: This pilot study evaluated adherence to anti-estrogen therapy in women with hormone receptor-positive breast cancer utilizing bubble packaging. METHODS: This was a single-arm prospective investigational pilot study that enrolled 86 patients between August 2012 and April 2014. Descriptive statistics for patient age, race, insurance, stage, duration of treatment, and comorbidities were computed. All patients received routine prescriptions in a "bubble" pack or daily blister pack dispensed by one pharmacy. Participants were considered adherent if they had taken ≥ 80% of the dispensed drug. Disease-free survival (DFS) and overall survival (OS) data were obtained at 78 months. RESULTS: Fifty patients were included in the analysis. The overall adherence rate was 97%. None of the variables examined (race, age, insurance status, and stage) had an impact on adherence rate. Only duration of endocrine therapy had a marginal effect on adherence (p value = 0.06). The late cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS was 94% and 5-year OS was 96%. There was no statistically significant difference in DFS and OS between patients with adherence rate > 90% and < 90%. CONCLUSION: Adherence rate to bubble packaging was higher than that in historical studies. Although this is a single-arm pilot study, these data suggest bubble packaging of anti-estrogen may be a reasonable option to improve adherence in hormone receptor-positive breast cancer patients.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Adesão à Medicação , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Resultado do TratamentoRESUMO
Advanced age is a risk factor for cancer and is attributed to dysregulation of the immune system. Historically, treatment of advanced cancer has primarily involved systemic chemotherapy that is associated with high treatment related toxicity especially in older adults. Immune checkpoint inhibitors (ICIs) provide an exciting treatment option for older adults in terms of efficacy and safety as compared to systemic chemotherapy. Given the pace of approval of ICIs for multiple cancers, there is an increase in both the use of ICIs and the associated immune-related adverse events. In this article, we address how to approach immunotherapy related toxicities in older adults given the availability of limited data.
Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoRESUMO
PURPOSE: To report early outcome analysis of a prospective institutional phase 2 trial of weekly hypofractionated breast irradiation (WHBI) for patients undergoing breast-conserving surgery (BCS). METHODS AND MATERIALS: Patients who underwent BCS for American Joint Committee on Cancer stage 0, I, or II breast cancer with negative surgical margins received whole-breast radiation therapy to 30 or 28.5 Gy in 5 weekly fractions with or without an additional boost. The eligibility criteria were the same as for NSABP (National Surgical Adjuvant Breast and Bowel Project) B39/RTOG (Radiation Therapy Oncology Group) 0413, and there were no restrictions on age, breast size, tumor grade, receptor status, or the use of cytotoxic chemotherapy for otherwise eligible patients. The primary endpoint was ipsilateral breast tumor recurrence. Patients were also evaluated for acute toxicity (Common Terminology Criteria for Adverse Events version 3.0), cosmesis (Harvard Scale), development of distant metastatic disease, and overall survival. RESULTS: Between January 2011 and October 2015, 158 eligible patients underwent WHBI immediately following BCS. The median age was 60 years (range, 30-84 years), and the median follow-up period was 3 years. Ipsilateral breast tumor recurrence developed in a total of 2 patients (1.3%), 1 in conjunction with widespread metastatic disease. Distant metastatic disease developed in 4 patients (2.5%), and the 3-year disease-free survival and overall survival rates were 97.5% and 96.2%, respectively. The most common grade 1 or 2 acute toxicities were breast pain, radiation dermatitis, and fatigue. There were 2 grade 3 events (1.3%): pain requiring narcotic analgesics (1) and posttreatment infection requiring hospitalization (1). The rate of excellent or good cosmesis versus fair or poor cosmesis was 82.3% versus 17.7%. The rate of significant cosmetic change from baseline to last follow-up (dropping from excellent or good to fair or poor) was 11.6%. CONCLUSIONS: Early outcomes after WHBI are favorable and parallel those seen with daily hypofractionated whole-breast irradiation. With broader entry criteria than all previous reports of WHBI, this study will facilitate comparison to the results of NSABP B39/RTOG 0413. With continued follow-up, future reports will assess cosmetic stability and disease-specific outcomes.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tamanho do Órgão , Hipofracionamento da Dose de Radiação , Radioterapia/efeitos adversos , Fatores de TempoRESUMO
OBJECTIVES: To compare the outcomes and toxicity of high-dose cisplatin (HDC) versus weekly cisplatin (WC) definitive chemoradiotherapy (CRT) for patients with human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (SCCOPx). METHODS: All patients with p16 positive SCCOPx treated with definitive CRT with cisplatin between 2010 and 2014 at a single institution were retrospectively reviewed. CTCAE v 4.03 toxicity criteria were used. The Kaplan-Meier method was used to estimate event-free survival (EFS) and the overall survival (OS). RESULTS: Of the 55 patients included, 22 were patients treated with HDC at dose of 100mg/m2 on days 1 and 22; and the remaining 33 patients were treated with WC at 40mg/m2. Both cohorts received a median total dose of cisplatin of 200mg/m2. At median follow-up of 31months, there was one local failure and no distant failures in the HDC cohort. In the WC group, there were 6 total failures (2 local, 4 distant). Estimated 2-year EFS was better in HDC cohort as compared to WC (96% vs. 75%; p=0.04). There was no significant difference in 2-year OS (95% vs. 94%; p=0.40). Weight loss, gastric tube dependence at six months, acute renal injury and grade 3 or 4 hematological toxicity were all similar between both groups. CONCLUSIONS: HPV-related SCCOPx treated with definitive CRT with either HDC or WC had similar toxicity profile. HDC had better EFS when compared with WC and this seems to be driven by increased distant failure rates, although the OS was similar.
Assuntos
Alphapapillomavirus/patogenicidade , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Orofaríngeas/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Escamosas/virologia , Relação Dose-Resposta a Droga , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/virologia , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Aging poses an unique opportunity to study cancer biology and treatment in older adults. Breast cancer is often studied in young women; however, much investigation remains to be done on breast cancer in our expanding elderly population. Diagnostic and management strategies applicable to younger patients cannot be empirically used to manage older breast cancer patients. Lack of evidence-based data continues to be the major impediment toward delivery of personalized cancer care to elderly breast cancer patients. This article reviews the relevant literature on management of curable breast cancer in the elderly, the role of geriatric assessment, complex treatment decision making within the context of patient's expected life expectancy, comorbidities, physical function, socioeconomic status, barriers to health care delivery, goals of treatment, and therapy-related side effects. Continuing efforts for enrolling elderly breast cancer patients in contemporary clinical trials, and thus improving age-appropriate care, are emphasized.
Assuntos
Neoplasias da Mama/terapia , Avaliação Geriátrica , Disparidades nos Níveis de Saúde , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Terapia Combinada , Comorbidade , Gerenciamento Clínico , Feminino , HumanosRESUMO
CONTEXT: To characterize a new conformation of hydrochlorothiazide (HCT) with better solubility and establishing its relationship with previously reported form I, obtained during attempted crystallization experiments. OBJECTIVE: The aim of present investigation is to unveil a new conformational polymorph (form IA) having a higher solubility compared to commercially available form I. MATERIALS AND METHODS: New form (IA) was obtained from slow evaporation as well as by solvent-antisolvent method and was then characterized by DSC, FTIR, PXRD and SCXRD. Equilibrium solubility profile shows that it is more soluble than form I. RESULTS: Appearance of phase transition endotherm at 215.87 °C in DSC spectra indicated the existence of new polymorph which was further confirmed by FTIR and PXRD. Single crystal study showed significant difference in various bond angles and torsion angles of the two forms. The solubility exhibited by form IA was (938 µg/mL) compared to form I (791 µg/mL) in water. DISCUSSION: Complete structural analysis and molecular arrangements in the unit cell along with the DSC and FTIR data confirm the existence of new conformer of HCT. CONCLUSION: This study reveals the existence of a new conformational polymorph of HCT molecule having higher solubility could prove to be promising in pre-formulation.
Assuntos
Hidroclorotiazida/análise , Hidroclorotiazida/química , Varredura Diferencial de Calorimetria/métodos , Conformação Molecular , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodosRESUMO
Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance to chemotherapies in cancer, thus representing an attractive target for an effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived ß-glucan, a natural polysaccharide compound, converts polarized alternatively activated macrophages or immunosuppressive TAM into a classically activated phenotype with potent immunostimulating activity. This process is associated with macrophage metabolic reprograming with enhanced glycolysis, Krebs cycle, and glutamine utilization. In addition, particulate ß-glucan converts immunosuppressive TAM via the C-type lectin receptor dectin-1-induced spleen tyrosine kinase-Card9-Erk pathway. Further in vivo studies show that oral particulate ß-glucan treatment significantly delays tumor growth, which is associated with in vivo TAM phenotype conversion and enhanced effector T cell activation. Mice injected with particulate ß-glucan-treated TAM mixed with tumor cells have significantly reduced tumor burden with less blood vascular vessels compared with those with TAM plus tumor cell injection. In addition, macrophage depletion significantly reduced the therapeutic efficacy of particulate ß-glucan in tumor-bearing mice. These findings have established a new paradigm for macrophage polarization and immunosuppressive TAM conversion and shed light on the action mode of ß-glucan treatment in cancer.
Assuntos
Polissacarídeos Fúngicos/farmacologia , Lectinas Tipo C/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/imunologia , Neoplasias Experimentais/tratamento farmacológico , Saccharomyces cerevisiae/química , beta-Glucanas/farmacologia , Animais , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/imunologia , Linhagem Celular Tumoral , Polissacarídeos Fúngicos/química , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Neoplasias Experimentais/genética , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , beta-Glucanas/químicaRESUMO
BACKGROUND: This study aimed to assess the efficacy and safety of chemoradiotherapy (CRT) for locally recurrent or advanced inoperable breast cancer. PATIENTS AND METHODS: Twenty patients treated between 2009 and 2013 were reviewed from a prospectively collected database. All patients had symptomatic recurrent or advanced breast cancer and had been deemed not to be ideal operative candidates. Treatment consisted of external beam radiotherapy to the primary tumor in the breast or regional lymph nodes, or both, concurrent with either capecitabine, paclitaxel, or cisplatin/etoposide chemotherapy. The grade of acute and late toxicity was evaluated, as was response to treatment, overall survival (OS), and local relapse-free survival (LRFS). RESULTS: Of the 20 patients, 9 (45%) presented with primary disease and 11 (55%) had recurrent disease. A total of 11 (55%) patients had evidence of metastatic disease. The overall clinical response rate was 100%, with a clinical complete response (CR) observed in 65% of patients and a clinical partial response (PR) observed in 35% of patients. At a median follow up of 25.3 months, 2-year LRFS was 73% and 2-year OS was 80%. Local control was significantly better in patients with an initial diagnosis (hazard ratio [HR], 0.139; 95% confidence interval [CI], 0.014-0.935) and in those who had not had previous in-field radiation (HR, 0.011; 95% CI, 0.005-0.512). The only grade ≥ 3 toxicity was acute dermatologic events (30%) and late dermatologic (15%) events. CONCLUSION: Concurrent CRT with capecitabine, paclitaxel, or cisplatin/etoposide for recurrent or advanced inoperable breast cancer is well tolerated with impressive clinical response rates and durable local control.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Quimiorradioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Terapia de Salvação/métodosRESUMO
OBJECTIVES: To analyze factors that influence the timing of adjuvant chemotherapy in patients who are candidates for breast-conservation therapy (BCT) but elect mastectomy with immediate reconstruction (M-IR). METHODS: We identified 35 consecutively treated patients with stage I or II breast cancer between 2004 and 2009 who underwent M-IR and adjuvant chemotherapy from the University of Louisville Cancer Registry. We matched these patients for age and AJCC stage to 35 controls who underwent BCT and adjuvant chemotherapy. We examined the timing and delay of initiation of chemotherapy using univariate logistic regression and McNemar test for matched pairs. RESULTS: For the 70 patients evaluated, the median age was 46 years (range, 30 to 65 y), and the distribution for stage I, IIA, and IIB was 22.9%, 65.7%, and 11.4%, respectively. The 2 groups were well balanced in terms of race, rural/urban status, smoking, diabetes, insurance coverage, and histology. For BCT and M-IR, the median time to chemotherapy initiation was 38 days (range, 25 to 103 d) and 55 days (range, 30 to 165 d), respectively. Patients undergoing M-IR were more likely to experience any delay (>45 d; 54.3% vs. 22.9%; P<0.001) and/or significant delay (>90 d; 20.0% vs. 2.9%; P<0.001). On univariate logistic regression analysis, surgery type had a major impact on delay of chemotherapy (odds ratio=8.35; 95% confidence interval, 2.86-24.4; P<0.001). CONCLUSIONS: The use of M-IR in breast-conservation candidates independently predicts for delay in initiation of adjuvant chemotherapy. Further study is needed to qualify the causes and clinical significance of these delays.
Assuntos
Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Mastectomia/métodos , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Idoso , Quimioterapia Adjuvante/métodos , Estudos de Coortes , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Modelos Logísticos , Análise por Pareamento , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of nonfunctional mature B cells in blood, bone marrow and lymphoid tissues. In the last decade, our understanding of CLL and consequently our diagnostic and therapeutic approaches have changed dramatically. Conventional fludarabine based chemotherapy has led to improved disease response and longer survival in young patients with CLL. However its application in elderly patients has been restricted by substantial myelosuppression and infection. Treatment of CLL is now moving towards targeted therapy. The success of new class of agents such as monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has sparked further search for treatment agents with novel targets to inhibit. The B cell receptor activating pathway involving the Bruton's tyrosine kinase (BTK) is crucial in B cell production and maintenance and is an attractive therapeutic target. Ibrutinib is an oral covalent inhibitor of the BTK pathway that induces apoptosis of B cells. Early phase studies with Ibrutinib either as a single agent or in combination regimens have shown promising results with an excellent safety profile in patients with high-risk, refractory or relapsed CLL and elderly treatment-naïve patients. This review summarizes the current knowledge of Ibrutinib in the treatment of CLL.