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PURPOSE OF REVIEW: Triple negative breast cancer is the most aggressive subtype of breast cancer and has traditionally lacked targeted therapies leading to worse prognosis in most patients. RECENT FINDINGS: We will review new targeted therapies for triple negative breast cancer including immunotherapy, antibody-drug conjugates, and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors. SUMMARY: Immunotherapy is now a backbone of PD-L1 positive metastatic triple negative breast cancer in the front-line setting as well as part of neoadjuvant therapy for high risk localized triple negative breast cancer. PARP inhibitors and a new antibody-drug conjugate are additional new therapies that can be used to improve the outcome for localized and metastatic triple negative breast cancers. None of these treatments were available before the review period for this paper.
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Imunoconjugados , Neoplasias de Mama Triplo Negativas , Humanos , Imunoconjugados/uso terapêutico , Imunoterapia , Terapia Neoadjuvante , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
PURPOSE OF REVIEW: The field of HER2-positive breast cancer has seen tremendous advances in the last 2 years with largest number of new drugs in decades. The present review aims to summarize the cutting-edge research of the past 2 years and future directions. RECENT FINDINGS: This review will go over four new drugs, three of which have gained FDA approval within the past 18 months, in the treatment of HER2-positive breast cancer. We will go over early and mature clinical data on these therapeutics and ongoing clinical trials further exploring their role in the treatment of patients with advanced HER2-positive breast cancer and HER2 low breast cancer. Will also discuss ongoing trials using immunotherapy and CDK4/6 inhibitors in the advanced HER2-positive setting. SUMMARY: : The therapies described in this review have quickly become standard of care for patients with HER2-positive breast cancer. Furthermore, they have the potential to change the landscape of breast cancer therapy further to include even patients with HER2 low breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Hormone receptor (HR) positive breast cancer represents the vast majority of breast cancer cases. Treatment for these patients has been 5 years of endocrine therapy in the localized setting and endocrine therapy alone in the metastatic setting until progression of disease and switch to chemotherapy until quite recently. RECENT FINDINGS: The current article will review recent data on role of extended endocrine therapy with tamoxifen and aromatase inhibitors and adjuvant bisphosphonates in the localized disease setting. It will then review the role of targeted agents such as cyclin dependent kinases 4/6 inhibitors, two of which were FDA approved in 2017 in the metastatic setting and are now standard of care. SUMMARY: Landscape of HR positive breast cancer is changing with doubling of progression-free survival with drugs approved in the last 2 years. Although antiestrogen therapy remains the backbone of therapy, we are continuing to improve outcome for patients by changes and additions to this therapy.
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Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Drogas em Investigação/uso terapêutico , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Mama/imunologia , Mama/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Terapia Combinada/tendências , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Drogas em Investigação/efeitos adversos , Antagonistas de Estrogênios/efeitos adversos , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/tendências , Prognóstico , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêuticoRESUMO
The incidence of breast cancer brain metastases has increased in recent years, largely due to improved control of systemic disease with human epidermal growth factor receptor 2 (HER2)-targeted agents and the inability of most of these agents to efficiently cross the blood-blood barrier (BBB) and control central nervous system disease. There is, therefore, an urgent unmet need for treatments to prevent and treat HER2+ breast cancer brain metastases (BCBMs). Aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway is frequently observed in many cancers, including primary breast tumors and BCBMs. Agents targeting key components of this pathway have demonstrated antitumor activity in diverse cancers, and may represent a new treatment strategy for BCBMs. In preclinical studies, several inhibitors of PI3K and mTOR have demonstrated an ability to penetrate the BBB and down-regulate PI3K signaling, indicating that these agents may be potential therapies for brain metastatic disease. The PI3K inhibitor buparlisib (BKM120) and the mTOR inhibitor everolimus (RAD001) are currently under evaluation in combination with trastuzumab in patients with HER2+ BCBMs.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Inibidores Enzimáticos/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase , Transdução de Sinais/efeitos dos fármacos , Animais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Receptor ErbB-2/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidoresRESUMO
BACKGROUND: The prevalence of vitamin D deficiency among patients with cancer has been previously reported. Because vitamin D is fat soluble, patients with pancreatic adenocarcinoma may have an especially high risk of vitamin D deficiency in association with ongoing and varying degrees of malabsorption. However, little is known about the correlation between vitamin D status and prognosis in these patients. METHODS: We conducted a retrospective review of vitamin D status in patients with pancreatic adenocarcinoma who were treated at Siteman Cancer Center. Patients' demographic information, clinical staging at the time of vitamin D assessment, vitamin D levels, and survival data were collected. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25[OH]D) level of less than 20 ng/mL, and vitamin D insufficiency was defined as a 25(OH)D level of between 20 ng/mL and 30 ng/mL. RESULTS: Between December 2007 and June 2011, 178 patients with pancreatic adenocarcinoma had their vitamin D levels checked at the time of initial visit at this center. Of these 178 patients, 87 (49%) had vitamin D deficiency, and 44 (25%) had vitamin D insufficiency. The median 25(OH)D level was significantly lower among nonwhite patients and among patients with stage I and II disease. A 25(OH)D level of less than 20 ng/mL was found to be associated with poor prognosis (p = 0.0019) in patients with stage III and IV disease. CONCLUSIONS: Vitamin D insufficiency and deficiency were prevalent among patients with pancreatic adenocarcinoma. The vitamin D level appears to be prognostic for patients with advanced pancreatic adenocarcinoma, and its effects should be further examined in a prospective study.
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Adenocarcinoma/complicações , Neoplasias Pancreáticas/complicações , Deficiência de Vitamina D/complicações , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Prognóstico , Modelos de Riscos Proporcionais , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Neoplasias PancreáticasRESUMO
Trastuzumab emtansine (T-DM1) is a novel antibody-drug conjugate, comprised of a potent cytotoxic drug connected via a stable linker to the anti-HER2 antibody, trastuzumab, thereby primarily targeting chemotherapy delivery to cells overexpressing the HER2 receptor. A Phase II randomized trial of T-DM1 in the front-line metastatic breast cancer setting revealed promising activity and improved safety compared with standard chemotherapy plus trastuzumab. Subsequently, a Phase III trial in patients with trastuzumab-pretreated metastatic breast cancer showed T-DM1 to be associated with prolonged progression-free and overall survival compared with lapatinib plus capecitabine. T-DM1 represents a major shift in the treatment of patients with breast cancer as it replaces traditional nontargeted chemotherapy with a 'smart' medication that directs the cytotoxic therapy to cancer cells by using a known biomarker.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Maitansina/análogos & derivados , Ado-Trastuzumab Emtansina , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos Hormonais/farmacocinética , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/metabolismo , Ensaios Clínicos como Assunto , Feminino , Humanos , Maitansina/farmacocinética , Maitansina/farmacologia , Maitansina/uso terapêutico , Receptor ErbB-2/metabolismo , Trastuzumab , Resultado do TratamentoRESUMO
PURPOSE: Amcenestrant (oral selective estrogen receptor degrader) demonstrated promising safety and efficacy in earlier clinical studies for endocrine-resistant, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (aBC). PATIENTS AND METHODS: In AMEERA-3 (ClinicalTrials.gov identifier: NCT04059484), an open-label, worldwide phase II trial, patients with ER+/HER2- aBC who progressed in the (neo)adjuvant or advanced settings after not more than two previous lines of endocrine therapy (ET) were randomly assigned 1:1 to amcenestrant or single-agent endocrine treatment of physician's choice (TPC), stratified by the presence/absence of visceral metastases, previous/no treatment with cyclin-dependent kinase 4/6 inhibitor, and Eastern Cooperative Oncology Group performance status (0/1). The primary end point was progression-free survival (PFS) by independent central review, compared using a stratified log-rank test (one-sided type I error rate of 2.5%). RESULTS: Between October 22, 2019, and February 15, 2021, 290 patients were randomly assigned to amcenestrant (n = 143) or TPC (n = 147). PFS was numerically similar between amcenestrant and TPC (median PFS [mPFS], 3.6 v 3.7 months; stratified hazard ratio [HR], 1.051 [95% CI, 0.789 to 1.4]; one-sided P = .643). Among patients with baseline mutated ESR1; (n = 120 of 280), amcenestrant numerically prolonged PFS versus TPC (mPFS, 3.7 v 2.0 months; stratified HR, 0.9 [95% CI, 0.565 to 1.435]). Overall survival data were immature but numerically similar between groups (HR, 0.913; 95% CI, 0.595 to 1.403). In amcenestrant versus TPC groups, treatment-emergent adverse events (any grade) occurred in 82.5% versus 76.2% of patients and grade ≥3 events occurred in 21.7% versus 15.6%. CONCLUSION: AMEERA-3 did not meet its primary objective of improved PFS with amcenestrant versus TPC although a numerical improvement in PFS was observed in patients with baseline ESR1 mutation. Efficacy and safety with amcenestrant were consistent with the standard of care for second-/third-line ET for ER+/HER2- aBC.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Receptores de Estrogênio/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2/metabolismoRESUMO
A 59-year-old woman presented with borderline resectable pancreatic adenocarcinoma involving the neck and body of the pancreas. She was treated with systemic chemotherapy followed by chemoradiation, with subsequent downstaging of the tumor by imaging. Subsequent resection had negative margins and negative lymph nodes with only microscopic disease present in the tumor specimen. Neoadjuvant therapy is controversial but could play a role in borderline resectable disease by allowing for higher chance of negative margins at surgery and increasing the chance for cure in these patients. Microscopic disease at time of resection is rare.
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Adenocarcinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/terapia , Quimiorradioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Pancreatectomia , Neoplasias Pancreáticas/terapia , Resultado do TratamentoRESUMO
CONTEXT: Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial. OBJECTIVE: The purpose of this study was to examine the tolerance and effectiveness of FOLFIRINOX as practiced outside of the confines of a clinical trial and to document any dose modifications used by practicing oncologists. METHODS: Data on patients with all stages of pancreatic adenocarcinoma treated with FOLFIRINOX at three institutions was analyzed for efficacy, tolerance, and use of any dose modifications. RESULTS: Total of 61 patients was included in this review. Median age was 58 years (range: 37 to 72 years), 33 were male (54.1%) and majority had ECOG performance of 0 or 1 (86.9%, 53 patients). Thirty-eight (62.3%) had metastatic disease, while 23 (37.7%) were treated for locally advanced or borderline resectable disease. Patients were treated with a median number of four cycles of FOLFIRINOX, with dose modifications in 58.3% (176/302) of all cycles. Ten patients had stable disease (16.4%), four had a partial response (6.6%) while eight had progressive disease (13.1%) on best imaging following therapy. Median progression-free survival and overall survival were 7.5 months and 13.5 months, respectively. The most common grade 3-4 adverse event was neutropenia at 19.7% (12 cases), with 4.9% (3 cases) rate of febrile neutropenia. Twenty-one patients (34.4%) were hospitalized as a result of therapy but there were no therapy-related deaths. Twenty-three (37.7%) had therapy eventually discontinued as a result of adverse events. CONCLUSION: Despite substantial rates of adverse events and use of dose modifications, FOLFIRINOX was found to be clinically effective in both metastatic and non-metastatic patients. Regimen toxicity did not detract from overall response and survival.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Dor Abdominal/induzido quimicamente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Relação Dose-Resposta a Droga , Esquema de Medicação , Fadiga/induzido quimicamente , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Resultado do TratamentoRESUMO
PURPOSE: Cardiac toxicity is a serious potential complication of HER2-directed therapies and anthracyclines. HER2 codon 655 and SLC28A3 gene polymorphisms have been reported to be associated with cardiac toxicity from anti-HER2 and anthracycline therapy, respectively. Association of the polymorphism at HER2 codon 655 with prognosis has also been reported. EXPERIMENTAL DESIGN: Whole blood samples from patients treated on a randomized adjuvant breast cancer trial (BCIRG-006) that compared chemotherapy with or without trastuzumab plus either anthracycline or nonanthracycline chemotherapy were tested for genetic polymorphisms in HER2 codon 655 and SLC28A3. Genotypes were correlated with cardiac function and disease-free survival (DFS) outcomes. RESULTS: Of 3,222 patients enrolled in BCIRG-006, 662 patient samples were successfully genotyped for the rs1136201 allele in HER2 (codon 655): 424 (64%) were AA, 30 (4.5%) were GG, and 208 (31%) were AG genotype. In addition, 665 patient samples were successfully genotyped for the rs7853758 allele in the SLC28A3 gene: 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG genotype. Follow-up time was 10 years. No correlation between DFS, cardiac event rate, or mean left ventricular ejection fraction (LVEF) and rs1136201 genotype was seen in the trastuzumab-treated or non-trastuzumab-treated patients. Moreover, mean LVEF and cardiac event rates were similar in all rs7853758 genotype groups treated with anthracycline-based therapy. CONCLUSIONS: In the largest study to date to evaluate whether two polymorphisms are associated with DFS and/or cardiac toxicity in HER2-positive breast cancer treated with trastuzumab and/or anthracyclines, we observed no correlation.
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Neoplasias da Mama , Cardiotoxicidade , Antraciclinas , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/genética , Feminino , Humanos , Polimorfismo Genético , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/uso terapêutico , Volume Sistólico , Trastuzumab/efeitos adversos , Função Ventricular EsquerdaRESUMO
PURPOSE: Guidelines support early integration of palliative care (PC) into standard oncology practice; however, little is known as to whether outcomes can be improved by modifying health care delivery in a real-world setting. METHODS: We report our 6-year experience of embedding a nurse practitioner in an oncology clinic (March 2014-March 2020) to integrate early, concurrent advance care planning and PC. RESULTS: Compared with patients with advanced cancer not enrolled in the palliative care nurse practitioner program, in March 2020, patients who are enrolled are more likely to have higher quality of PC (eg, goals of care note documentation [82% v 15%; P < .01], referral to the psychosocial oncology program [67% v 37%; P < .01], and referral to hospice [61% v 34%; P < .01]) and less inpatient utilization in the last 6 months of life (eg, hospital days [12 v 18; P < .01] and intensive care unit days [1.2 v 2.3; P < .01]). The program expanded over time with the support of faculty skills training for advance care planning and PC, supporting a shared mental model of PC delivery within the oncology clinic. CONCLUSION: Embedding a trained palliative care nurse practitioner in oncology clinics to deliver early integrated PC can lead to improved quality of care for patients with advanced cancer.
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Neoplasias , Profissionais de Enfermagem , Humanos , Oncologia , Neoplasias/psicologia , Neoplasias/terapia , Cuidados Paliativos , Melhoria de QualidadeAssuntos
Indóis/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Sulfonamidas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Anaplásico da Tireoide , VemurafenibRESUMO
BACKGROUND: Stomatitis is a frequent dose limiting toxicity of everolimus, an approved therapy for patients with metastatic breast cancer. No randomized trials of a prophylactic measure to prevent mucositis have been reported. METHODS: We conducted a phase II, open-label trial in which patients with metastatic breast cancer starting everolimus were randomized to best supportive care (BSC) versus prophylactic use of an oral mucoadhesive, non-steroid containing mouth wash. The primary endpoint was rate of any grade stomatitis as reported by the treating physicians. Secondary endpoints were severity of stomatitis according to the Oral Mucositis Assessment Scale (OMAS) and rates of everolimus dose reduction or discontinuation due to mucositis. RESULTS: Of 61 evaluable patients, 32 were randomized to and treated with oral mucoadhesive and 29 with BSC. Any grade stomatitis developed in 46.9% (15/32) of study arm and 65.5% (19/29) of BSC arm patients (p = 0.14). The difference between the two arms was significantly in favor of the mucoadhesive arm when mucositis was scored according to the OMAS with average score of 0.3 in study arm versus 0.5 in the control arm (p = 0.03). There were fewer dose adjustments or therapy discontinuations in the study arm compared with BSC (16% versus 31%, respectively) but the difference did not reach statistical significance. CONCLUSION: Here we provide early evidence from the first randomized trial supporting the use of oral prophylactic mucoadhesive for everolimus-associated stomatitis. A trial comparing prophylactic oral mucoadhesive to steroid mouth wash may be warranted.
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Breast sarcomas are exceptionally rare mesenchymal neoplasms composed of many histologic subtypes. Therapy is guided by principles established in the management of extremity sarcomas. The anatomic site does influence treatment decisions, particularly the surgical management. Surgery should be undertaken with the aim of achieving a widely negative margin. Selected patients can be managed with breast-conserving surgery. Breast reconstruction is increasingly being undertaken for selected patients. Radiation therapy and chemotherapy are used selectively for large, high-grade sarcomas for which there is significant concern for local and distant recurrence.
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Neoplasias da Mama/terapia , Gerenciamento Clínico , Sarcoma/terapia , Terapia Combinada , Feminino , HumanosRESUMO
In February 2013, ado-trastuzumab emtansine (T-DM1, Kadcyla®) received regulatory approval in the United States for treatment-refractory human epidermal growth factor receptor 2 (HER2) positive metastatic or locally advanced breast cancer based on results from EMILIA, a large phase III trial that compared standard of care lapatinib plus capecitabine to T-DM1. Several other studies have been reported in the metastatic setting and multiple trials are ongoing or planned in the neoadjuvant, adjuvant and advanced disease settings. Here we provide an updated and comprehensive review of clinical trials evaluating T-DM1, discuss management of toxicity associated with this drug, propose potential mechanisms of resistance and offer practical considerations for the treating oncologist.
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Although there has been a significant progress in the recognition and management of the most common chemotherapy side effects, there is limited data on CNS toxicities. Since CNS toxicities can cause significant morbidity and delay or interruption of potentially effective therapies, there is a need for better understanding, early detection, prompt discontinuation of the offending drug, and use of antidotes when available. This review describes neurological toxicities from some of the commonly used chemotherapy agents.
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Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Central/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Antineoplásicos/uso terapêutico , Cisplatino/efeitos adversos , Citarabina/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Ifosfamida/efeitos adversos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Vincristina/efeitos adversosRESUMO
The mammalian target of rapamycin (mTOR) inhibitor class of drugs represents the newest addition to the armamentarium of therapies for hormonally driven breast cancer. It has recently been shown that the addition of mTOR inhibitor everolimus to aromatase inhibitors in hormone receptor-positive breast cancers improves progression-free survival. However, a clinically significant toxicity associated with this class of drugs is the development of noninfectious pneumonitis (NIP). Although generally mild and manageable, everolimus-induced NIP requires prompt diagnosis and management. This article will provide a brief overview of data relating to dysregulation of the phosphatidylinositol-3-kinase/protein kinase B/mTOR pathway in breast cancer; review the literature relating to the efficacy and safety of mTOR inhibitors in breast cancer; and evaluate the incidence, severity, and optimal management of mTOR inhibitor-related NIP in breast cancer.
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Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Pneumonia/induzido quimicamente , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Tosse/induzido quimicamente , Dispneia/induzido quimicamente , Elafina/antagonistas & inibidores , Everolimo , Feminino , Humanos , Incidência , Pneumonia/diagnóstico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversosRESUMO
In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established fertility preservation strategy, providing a 25-35% chance of pregnancy. In addition, oocyte freezing can be considered as an alternative in patients who are single and in those who do not wish a sperm donor. Although ovarian tissue harvesting appears to be safe, experience regarding ovarian transplantation is still limited due to low utilization, so the true value of this procedure remains to be determined. Nevertheless, in clinical situations in which chemotherapy needs to be started in young patients facing premature ovarian failure, ovarian tissue preservation seems to be a promising option for restoring fertility, especially in conjunction with other options like immature oocyte retrieval, in vitro maturation of oocytes, oocyte vitrification, or embryo cryopreservation. It seems that in vitro maturation is a useful strategy because it improves oocyte or cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.
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Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Preservação da Fertilidade/métodos , Fertilidade/efeitos dos fármacos , Infertilidade Feminina/induzido quimicamente , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Humanos , GravidezRESUMO
BACKGROUND: The standard of care in patients with metastatic pancreatic adenocarcinoma is undefined beyond second line of treatment. There have been scant reports of benefit from nab-paclitaxel in patients with refractory pancreatic cancer. MATERIALS AND METHODS: A retrospective review was carried out in patients with pancreatic adenocarcinoma at Siteman Cancer Center, who had received nab-paclitaxel monotherapy after experiencing disease progression on standard treatments. Nab-paclitaxel was given either two out of every three weeks or three out of every four weeks. RESULTS: Twenty patients were identified and included for data analysis. Median age was 63.5 years old. All patients had previously received gemcitabine, while 40% had also received FOLFIRINOX. Median number of prior lines of systemic treatment was 2. Patients were treated for a median of 15 weeks, with a range of 1 to 41.7 weeks. Median dose of nab-paclitaxel was 100 mg/m(2) with range of 75-125 mg/m(2). Best response imaging was available in 17 patients and 11 out of the 17 patients (64.7%) had stable disease. Median progression-free survival (PFS) was 3.7 months and overall survival (OS) were 5.2 months. Most common treatment related toxicities included grade 1 pneumonitis in five patients (25%), grade 3 or 4 neutropenia in three patients (15%), and dehydration resulting in hospitalization in one patient (5%). CONCLUSIONS: Nab-paclitaxel monotherapy had acceptable level of toxicity in a heavily pretreated patient population with pancreatic cancer and appeared to provide a clinical benefit. This agent is worthy of further prospective studies to evaluate extent of benefit after standard therapies have failed.
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OBJECTIVES: The study objectives were to evaluate the safety, tolerability, and preliminary efficacy of multiple doses of dulanermin in combination with modified FOLFOX6 and bevacizumab in previously untreated patients with locally advanced, recurrent, or metastatic colorectal cancer. PATIENTS AND METHODS: A total of 23 patients received dulanermin at dosages of 4.5 or 9 mg/kg/d given on days 1 to 3 of each 14-day cycle along with standard dosing of modified FOLFOX6 plus bevacizumab. Dose-limiting toxicities, adverse events (AEs), maximum tolerated dose, and response according to Response Evaluation Criteria in Solid Tumors were assessed. RESULTS: In the first cohort (3 patients given dulanermin at 4.5 mg/kg/d) and second cohort (6 patients given dulanermin at 9 mg/kg/day), no dose-limiting toxicities were observed. The subsequent 14 patients were treated with a dulanermin dosage of 9 mg/kg/d. Patients (N = 23) received 2 to 42 cycles of dulanermin (median 15). The most common grade 3 or 4 AEs were neutropenia (39%), hypertension (17%), peripheral neuropathy (17%), hand-foot syndrome (13%), and pulmonary embolism (13%). Three patients (13%) discontinued the study because of serious AEs. Overall, a best response of partial response was observed in 13 patients (57%) (9 confirmed, 4 unconfirmed), stable disease was observed in 7 patients (30%), and disease progression was observed in 3 patients (13%). The median progression-free survival was 9.9 months (95% confidence interval, 7.0-12.7). CONCLUSIONS: Overall, the addition of dulanermin to first-line FOLFOX plus bevacizumab was well tolerated in patients with advanced colorectal cancer, with similar AEs that would be expected from FOLFOX plus bevacizumab. A randomized study is required to assess the clinical efficacy of dulanermin in this patient population.