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1.
Ann Pharmacother ; : 10600280231197459, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700573

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of the novel KRAS-targeting agents, sotorasib and adagrasib, in treating KRAS G12C-mutated non-small cell lung cancer (NSCLC). DATA SOURCES: A comprehensive English-based literature search of PubMed and Clinicaltrials.gov between January 2000 and July 2023 was conducted using the terms sotorasib, Lumakras, AMG 510, adagrasib, Krazati, and MRTX849. STUDY SELECTION AND DATA EXTRACTION: Relevant prescribing information, clinical trials, and treatment guidelines were evaluated. DATA SYNTHESIS: Sotorasib and adagrasib received accelerated US Food and Drug Administration (FDA) approval following pivotal phase I/II clinical trials. Sotorasib, a first-in-class KRAS inhibitor, demonstrated an overall response rate (ORR) of 41% and a progression-free survival (PFS) of 6.3 months. In a phase III confirmatory trial, sotorasib showed significantly longer PFS compared with docetaxel (5.6 vs. 4.5 months; P = 0.0017). Adagrasib produced an ORR of 42.9% and a PFS of 6.5 months. Both drugs present unique safety profiles, with common toxicities, including diarrhea, musculoskeletal pain, fatigue, and hepatotoxicity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: With KRAS mutations being among the most common oncogenic alterations in NSCLC, sotorasib and adagrasib offer new therapeutic avenues for this previously "undruggable" target. Current treatment guidelines list sotorasib and adagrasib as second-line options in patients with confirmed KRAS G12C-mutated NSCLC. Additional studies are required to further differentiate the safety and efficacy profiles of these 2 agents and identify their optimal place in therapy. CONCLUSION: Sotorasib and adagrasib demonstrated promising outcomes in targeting the constitutively active KRAS G12C oncogenic driver, underscoring the need for further research to optimize their therapeutic application in this high-risk population.

2.
Curr Oncol Rep ; 25(4): 379-386, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36808556

RESUMO

PURPOSE OF REVIEW: There is a paucity of evidence for managing perioperative anticoagulation in patients with cancer. This review aims to provide clinicians who provide care for patients with cancer an overview of the available information and strategies needed to provide optimal care in a perioperative setting. RECENT FINDINGS: There is new evidence available around the management of perioperative anticoagulation in patients with cancer. The new literature and guidance were analyzed and summarized in this review. Management of perioperative anticoagulation in individuals with cancer is a challenging clinical dilemma. The approach to managing anticoagulation requires clinicians to review both disease and treatment specific patient factors that can contribute to both thrombotic and bleed risks. A thorough patient-specific assessment is essential in ensuring patients with cancer receive appropriate care in the perioperative setting.


Assuntos
Neoplasias , Trombose , Humanos , Anticoagulantes/uso terapêutico , Assistência Perioperatória , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Trombose/etiologia , Trombose/prevenção & controle , Trombose/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico
3.
Ann Pharmacother ; 57(7): 867-879, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36349896

RESUMO

OBJECTIVE: To provide an overview of clinical sequelae and emerging treatment options for hemophagocytic lymphohistiocytosis (HLH). DATA SOURCES: A literature search was conducted using the search terms "hemophagocytic lymphohistiocytosis," "hemophagocytic syndrome," "macrophage activation syndrome," and "treatment" on Ovid and PubMed from January 1, 2017, through September 28, 2022. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical trials, meta-analyses, case reports, review articles, package inserts, and guidelines to identify current and emerging therapeutic options for the management of HLH. DATA SYNTHESIS: Genetic disorders and secondary causes may trigger HLH in both children and adults. Notable improvements in the diagnosis of HLH were seen with implementation of the HLH-2004 standard diagnostic criteria; however, timely and accurate identification of HLH remain significant barriers to optimal management. Multiagent immunochemotherapy are the backbone of aggressive therapy for acutely ill patients with HLH. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The global coronavirus 2019 (COVID-19) pandemic and emerging immune effector cell therapies have served to highlight the concerns with immune dysregulation and subsequent HLH precipitation. Without prompt identification and treatment, HLH can be fatal. Historically, the clinician's armamentarium for managing HLH was sparse, with etoposide-based protocols serving as the standard of care. Relapsed or refractory disease portends a poor prognosis and requires additional treatment options. Second- or subsequent-line options now include hematopoietic stem cell transplantation, emapalumab, alemtuzumab, anakinra, ruxolitinib, and tocilizumab. CONCLUSIONS: Improvements in diagnostic methods and novel immunosuppressive treatment strategies, including noncytotoxic immunochemotherapy, have transformed the therapeutic landscape. Unfortunately, many unanswered questions remain. Additional studies are required to optimize dosing, schedules, treatment sequences, and indications for novel treatment options.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Criança , Adulto , Humanos , Linfo-Histiocitose Hemofagocítica/terapia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , COVID-19/terapia , COVID-19/complicações , Imunossupressores/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
4.
J Oncol Pharm Pract ; 29(1): 162-169, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34918554

RESUMO

INTRODUCTION: Simulation and gamification are two popular educational tools utilized to enhance student learning and engagement. This study aimed to evaluate the effectiveness of integrating a hybrid cancer clinic simulation into the curricula for third-year pharmacy (P3) students. METHODS: This prospective, single-arm pilot study incorporated a mixed-method learning activity involving patient simulation and escape room elements. Two cancer clinic simulations were developed by faculty members. For each clinic, students were randomly divided into 6 groups and tasked with completing a series of Pharmacist Patient Care Process (PPCP) activities involving patient actors. The PPCP activities were interwoven with engaging puzzles and games to simulate an escape room. Student learning and retention was measured by pre- and post-simulation quizzes and course level exams. A perceptions survey was administered after each simulation activity. RESULTS: Thirty-six students participated in both cancer clinic simulations, with 100% completing all aspects of the study. Mean student quiz scores improved from 61.4% to 81.7% (p < 0.0001) and 52.6% to 81.8% (p < 0.0001) following the first and second simulations, respectively. Exam performance improved for 16 out of 19 exam questions, with a significant increase in 4 questions (p < 0.05). Students overwhelmingly agreed that the cancer clinic simulations 1) reinforced knowledge, 2) facilitated PPCP, 3) improved their ability to make chemotherapeutic recommendations, 4) enhanced problem-solving skills, and 5) encouraged collaboration. CONCLUSION: This innovative hybrid simulation enhanced oncology-related knowledge and supported an interactive environment that improved student confidence and teamwork. Students enjoyed the simulations and recommended continuation for all future cohorts.


Assuntos
Educação em Farmácia , Neoplasias , Humanos , Currículo , Educação em Farmácia/métodos , Avaliação Educacional/métodos , Neoplasias/terapia , Projetos Piloto , Estudos Prospectivos , Simulação de Paciente
5.
Ann Pharmacother ; 57(5): 585-596, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35962528

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of tisotumab vedotin-tftv (TV), a first-in-class vectorized anti-tissue factor (TF) antibody-drug conjugate (ADC), for the treatment of recurrent or metastatic cervical cancer. DATA SOURCES: A literature search of ClinicalTrials.gov, Embase, and PubMed was conducted using the terms tisotumab vedotin AND cervical cancer from inception to June 30, 2022. STUDY SELECTION AND DATA EXTRACTION: All applicable publications, package inserts, meeting abstracts, and clinical trials involving TV in the treatment of cervical cancer were reviewed. DATA SYNTHESIS: TV is a fully human TF-specific monoclonal antibody conjugated to monomethyl auristatin E, which serves as a highly potent cytotoxic payload. In the pivotal phase II InnovaTV 204 clinical trial, TV demonstrated an objective response rate of 24% (95% confidence interval [CI], 16%-33%). The mean duration of response was 8.3 months. Common toxicities included abdominal pain, alopecia, conjunctivitis, constipation, decreased appetite, diarrhea, dry eye, epistaxis, nausea/vomiting, and peripheral neuropathy. Unique and/or serious adverse events warranting careful monitoring include ocular complications, hemorrhaging, peripheral neuropathies, fetal-embryo toxicity, pneumonitis, and immunogenicity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Recurrent or metastatic cervical cancer remains a high-risk disease with limited treatment options. Using ADCs to target tumors with aberrant expression of TF appears to be a viable treatment strategy. CONCLUSIONS: TV is the first Food and Drug Administration-approved TF-directed ADC. With a manageable safety profile and promising anticancer activity, TV warrants consideration as a novel targeted agent for the treatment of recurrent or metastatic cervical cancer. Further studies are required to determine the optimal place in therapy for TV.


Assuntos
Antineoplásicos , Imunoconjugados , Doenças do Sistema Nervoso Periférico , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais/efeitos adversos , Imunoconjugados/efeitos adversos
6.
Ann Pharmacother ; 56(6): 716-726, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34541874

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). DATA SOURCES: An English-based literature search of PubMed, EMBASE, and ClinicalTrials.gov was conducted using the terms selumetinib AND neurofibromatosis from inception to August 1, 2021. STUDY SELECTION AND DATA EXTRACTION: Relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review. DATA SYNTHESIS: The open-label, multicenter, single-arm, phase II SPRINT trial demonstrated clinically significant improvements in PN-related complications. Of 50 symptomatic patients, 68% experienced a partial response, with a median change in tumor volume of -27.9% from baseline. Estimated progression-free survival at 3 years was 84%. Additionally, clinically meaningful improvements were seen on patient- and parent-reported assessments evaluating pain, range of motion, disfigurement, and quality of life. Overall, the adverse effect profile for selumetinib appears mild and manageable. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Selumetinib is the first FDA-approved treatment for inoperable PN in patients with NF1, demonstrating that MEK inhibition is a promising therapeutic strategy. Studies are ongoing to assess the effect of selumetinib on other NF1-associated tumor types and to determine the optimal dosing schedule and treatment duration. Cost and treatment burden must be considered when selecting selumetinib therapy. CONCLUSION: Selumetinib exhibits impressive antitumor activity and sustained clinical benefit in patients lacking other viable treatment options. Further studies are warranted to determine the optimal age of initiation, treatment duration, and overall cost-effectiveness of selumetinib.


Assuntos
Neurofibroma Plexiforme , Neurofibromatose 1 , Benzimidazóis , Humanos , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico , Estudos Multicêntricos como Assunto , Neurofibroma Plexiforme/complicações , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/patologia , Neurofibromatose 1/complicações , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/patologia , Qualidade de Vida
7.
Ann Pharmacother ; 56(5): 609-619, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34340597

RESUMO

OBJECTIVE: To identify and assess the current literature surrounding the safety, efficacy, and practical considerations of brexucabtagene autoleucel (brexu-cel) for the treatment of relapsed or refractory (r/r) mantle cell lymphoma (MCL). DATA SOURCES: An English-based literature search was conducted using the terms "brexucabtagene autoleucel" AND "mantle cell lymphoma" OR "KTE-X19"in PubMed (inception through May 1, 2021), EMBASE (inception through May 1, 2021), and ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: All studies evaluating the use of brexu-cel in MCL were considered for inclusion. DATA SYNTHESIS: In the pivotal ZUMA-2 trial, brexu-cel demonstrated objective response and complete response rates of 85% and 59%, respectively. These results were consistent among high-risk subgroups. Noteworthy treatment-related adverse effects included grade ≥3 cytopenias (94%), immune effector cell-associated neurotoxicity syndrome (31%), and cytokine release syndrome (15%). Brexu-cel elicited a toxicity profile similar to that of other novel chimeric antigen receptor (CAR) T-cell products, with no new safety signals. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: There are currently no head-to-head clinical trials evaluating brexu-cel against other approved subsequent-line options in r/r MCL. In a relatively small phase II trial, brexu-cel demonstrated impressive response rates in heavily pretreated patients, with few viable alternatives. Long-term safety and efficacy outcomes with brexu-cel are unknown. The prevention, identification, and management of unique CAR T-cell toxicities requires expert care from a well-trained interdisciplinary team. CONCLUSION: Brexu-cel has emerged as a viable treatment option in MCL. Additional studies are required to determine the optimal sequencing and place in therapy for brexu-cel in this highly heterogeneous, pathobiologically distinct, and incurable malignancy.


Assuntos
Imunoterapia Adotiva , Linfoma de Célula do Manto , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Ensaios Clínicos como Assunto , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfoma de Célula do Manto/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico
8.
Am J Hosp Palliat Care ; 39(3): 274-281, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34169763

RESUMO

BACKGROUND: Hospice patients are frequently confronted with potentially infectious complications necessitating antibiotic consideration. Information regarding the appropriate use of antibiotics and their impact on symptom management in hospice patients are unknown. OBJECTIVES: This study aimed to evaluate and describe the use of an antibiotic initiation tool in patients admitted to outpatient hospice services. The primary outcome assessed the percentage of antibiotics that were appropriately initiated based on Loeb's Minimum Criteria (LMC) for Antibiotic Initiation Tool. Secondary outcomes included the number of patients with documented symptom resolution following antibiotic completion, the number of antibiotic courses that were successfully completed, and treatment-related adverse events. METHODS: This was a retrospective, multisite, descriptive analysis of hospice patients treated with antibiotics between April 2019 and September 2020. RESULTS: Two hundred and thirty patients were assessed for inclusion, with 172 meeting eligibility criteria and receiving a total of 201 antibiotic courses. Based on LMC, 84 of the 201 (42%) antibiotics ordered were appropriate, with 60% of these LMC-approved courses resulting in symptom resolution. Out of 201 total courses, 99 (49%) resulted in symptom resolution. Overall, 160 (80%) antibiotic courses were successfully completed. CONCLUSION: In this study, antibiotic initiation in hospice patients frequently did not meet LMC. Less than half of the antibiotics prescribed led to symptom resolution despite antibiotic course completion in most patients. There is no consensus or guidelines directing appropriate antibiotic decision-making in hospice patients. The appropriate use of antibiotics in terminally ill patients warrants additional research.


Assuntos
Antibacterianos , Cuidados Paliativos na Terminalidade da Vida , Antibacterianos/uso terapêutico , Humanos , Cuidados Paliativos , Estudos Retrospectivos
9.
J Oncol Pharm Pract ; 28(5): 1056-1062, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34027747

RESUMO

INTRODUCTION: The primary objective of this study was to evaluate the effectiveness of an autonomous oncology boot camp on Advanced Pharmacy Practice Experience (APPE) student knowledge. Secondary objectives included assessing student perception of the virtual learning experience and overall comfort level with the material. METHODS: APPE students rotating through our institution between November 2019 and March 2020 were voluntarily enrolled in a 4-hour oncology-focused boot camp, which included five PlayPosit (Denver, CO, USA) interactive video lectures embedded with case-based application questions followed by one comprehensive web-based Quandary (Victoria, BC, Canada) action-maze case. Student learning was measured by a pre- and post-intervention exam. A web survey tool (Qualtrics, Provo, UT, USA) collected student perceptions evaluating their comfort with oncology-specific drug knowledge and APPE rotations tasks. RESULTS: Fifty students enrolled in the oncology boot camp, with 100% completing the pre- and post-intervention assessments. Overall, pre-intervention exam scores (mean: 55.4%, SD: 21.8%) improved by 23.2% following the boot camp (mean: 78.6%, SD: 19.2%; p < 0.001). Students performed better on all 10 exam questions, with 6 questions showing a statistically significant improvement (p < 0.05). Forty-five students (90%) completed the perception surveys. Of those, 93% agreed that it effectively reinforced important oncology knowledge, 91% supported the autonomous design, and 82% would recommend the oncology boot camp for future students. CONCLUSION: The boot camp proved to be a beneficial educational tool that enhanced student knowledge and confidence in navigating common oncology concepts. Students valued the ability to independently complete the activities and supported its continuation.


Assuntos
Farmácia , Estudantes de Farmácia , Humanos , Avaliação Educacional , Currículo , Oncologia
10.
Ann Pharmacother ; 55(12): 1486-1501, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33771051

RESUMO

OBJECTIVE: To provide an overview of clinical recommendations regarding genomic medicine relating to pain management and opioid use disorder. DATA SOURCES: A literature review was conducted using the search terms pain management, pharmacogenomics, pharmacogenetics, pharmacokinetics, pharmacodynamics, and opioids on PubMed (inception to February 1, 2021), CINAHL (2016 through February 1, 2021), and EMBASE (inception through February 1, 2021). STUDY SELECTION AND DATA EXTRACTION: All relevant clinical trials, review articles, package inserts, and guidelines evaluating applicable pharmacogenotypes were considered for inclusion. DATA SYNTHESIS: More than 300 Food and Drug Administration-approved medications contain pharmacogenomic information in their labeling. Genetic variability may alter the therapeutic effects of commonly prescribed pain medications. Pharmacogenomic-guided therapy continues to gain traction in clinical practice, but a multitude of barriers to widespread pharmacogenomic implementation exist. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Pain is notoriously difficult to treat given the need to balance safety and efficacy when selecting pharmacotherapy. Pharmacogenomic data can help optimize outcomes for patients with pain. With improved technological advances, more affordable testing, and a better understanding of genomic variants resulting in treatment disparities, pharmacogenomics continues to gain popularity. Unfortunately, despite these and other advancements, pharmacogenomic testing and implementation remain underutilized and misunderstood in clinical care, in part because of a lack of health care professionals trained in assessing and implementing test results. CONCLUSIONS: A one-size-fits-all approach to pain management is inadequate and outdated. With increasing genomic data and pharmacogenomic understanding, patient-specific genomic testing offers a comprehensive and personalized treatment alternative worthy of additional research and consideration.


Assuntos
Preparações Farmacêuticas , Farmacogenética , Humanos , Dor/tratamento farmacológico , Dor/genética , Manejo da Dor , Testes Farmacogenômicos
11.
Ann Pharmacother ; 55(10): 1236-1253, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33435716

RESUMO

OBJECTIVE: To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL). DATA SOURCES: We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: blinatumomab, Blincyto, lymphoblastic leukemia, and bispecific T-cell engager. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion. DATA SYNTHESIS: Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in "chemotherapy-free" combination regimens. CONCLUSIONS: Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão
12.
Ann Pharmacother ; 55(4): 466-479, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32762363

RESUMO

OBJECTIVE: To evaluate the current literature for tisagenlecleucel in the treatment of relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search of PubMed (inception to June 18, 2020) and ClinicalTrials.gov was conducted using the following search terms: CTL019, chimeric antigen receptor, CAR-T, and tisagenlecleucel. STUDY SELECTION AND DATA EXTRACTION: All trials evaluating the use of tisagenlecleucel in B-cell ALL were reviewed and considered for inclusion. DATA SYNTHESIS: Tisagenlecleucel displayed overall remission rates ranging from 69% to 93% in patients who historically respond extremely poorly to salvage therapy. Remissions were durable, with 12-month relapse-free survival (RFS) rates of 55% to 59%. These promising results are tempered by the unique adverse effect profile of chimeric antigen receptor (CAR) T-cell therapy. Potentially life-threatening cytokine release syndrome (CRS) occurred in 77% to 100% of patients, and immune effector cell-associated neurotoxicity syndrome (ICANS) developed in 31% to 45% of patients receiving tisagenlecleucel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The successful utilization of tisagenlecleucel therapy requires meticulous planning, prudent patient selection, multidisciplinary collaboration, and expert training to ensure optimal patient care. The complex interplay of patient- and treatment-related factors creates problematic barriers that must be expertly navigated by the health care team and authorized treatment center. CONCLUSIONS: As the first US Food and Drug Administration-approved gene therapy, tisagenlecleucel heralds an immunotherapeutic breakthrough for treating pediatric and young adult patients with r/r B-cell ALL. Many questions surrounding patient-specific gene and cellular therapies remain, but their transformative potential in cancer care remains promising.


Assuntos
Terapia Genética/métodos , Imunoterapia Adotiva/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/administração & dosagem , Receptores de Antígenos Quiméricos/antagonistas & inibidores , Animais , Doença Crônica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia , Recidiva , Terapia de Salvação/métodos
13.
Ann Pharmacother ; 55(3): 390-405, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32698673

RESUMO

OBJECTIVE: To evaluate the literature for axicabtagene ciloleucel (axi-cel), a first-in-class chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL). DATA SOURCES: We conducted a PubMed (inception to June 22, 2020) and ClinicalTrials.gov search using the following terms: CD19, chimeric antigen receptor, and lymphoma. STUDY SELECTION AND DATA EXTRACTION: All retrospective and prospective studies evaluating the use of axi-cel in LBCL were reviewed. DATA SYNTHESIS: In the pivotal ZUMA-1 trial, axi-cel exhibited unprecedented overall and complete response rates of 83% and 58%, respectively. With a median follow-up of 27.1 months, 39% of patients had ongoing responses. Furthermore, postmarketing retrospective analyses found similar response rates in a more clinically diverse LBCL patient population. Novel CAR T-cell therapy elicits unique and potentially life-threatening toxicities that include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Studies reported grade ≥3 CRS in 7% to 14% of patients and grade ≥3 ICANS in 31% to 55% of patients. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Axi-cel was the first US Food and Drug Administration-approved genetically engineered autologous CAR T-cell agent in r/r LBCL, representing an important milestone and paradigm shift in cancer treatment. Adoptive T-cell immunotherapy is a breakthrough treatment modality requiring careful patient selection, multidisciplinary collaboration, comprehensive patient counseling, and expert training to ensure optimal treatment. CONCLUSIONS: The initial and ongoing results with axi-cel are encouraging, but long-term safety and efficacy data are lacking. Additional studies are required to identify axi-cel's ideal place in LBCL therapy.


Assuntos
Antígenos CD19/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Receptores de Antígenos Quiméricos/metabolismo , Antígenos CD19/farmacologia , Produtos Biológicos , Humanos , Linfoma Difuso de Grandes Células B/patologia , Estudos Prospectivos , Recidiva , Estudos Retrospectivos
14.
Ann Pharmacother ; 55(6): 772-782, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32945172

RESUMO

OBJECTIVE: To evaluate the pharmacology, pharmacokinetics, clinical efficacy, safety, dosing, cost, and clinical implications of enfortumab vedotin-ejfv (EV) in the treatment of locally advanced or metastatic urothelial carcinoma (UC). DATA SOURCES: A literature search of PubMed (inception to August 2020) was conducted using the terms enfortumab, vedotin, Padcev, and Nectin. Data were also obtained from package inserts, meeting abstracts, and ongoing studies from ClinicalTrials.gov. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles, package inserts, and meeting abstracts evaluating EV for the treatment of UC were analyzed. DATA SYNTHESIS: Antibody-drug conjugates (ADCs) deliver potent cytotoxic agents using highly selective monoclonal antibodies. Targeting the near-universal expression of Nectin-4 on UC cells is a viable therapeutic strategy. In a pivotal phase II trial, EV demonstrated an overall response rate of 44%, and a median duration of response of 7.6 months. Estimated overall survival was 11.7 months with a median estimated progression-free survival of 5.6 months. Results were similar among difficult-to-treat patients, including those with liver metastases. Unique toxicity concerns with EV require careful consideration and monitoring. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: EV, a first-in-class anti-Nectin-4 ADC, provides impressive response rates with manageable toxicities, making it a promising treatment option for patients with multiply relapsed or refractory UC. CONCLUSION: The US Food and Drug Administration-approved EV demonstrates antitumor activity in heavily pretreated patients with UC but harbors important adverse effects and financial concerns. Additional studies are required to identify the optimal sequencing, patient population, and place in therapy for EV.


Assuntos
Carcinoma de Células de Transição , Imunoconjugados , Preparações Farmacêuticas , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Anticorpos Monoclonais , Humanos
15.
Int J Pharm Compd ; 19(4): 344-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26625573

RESUMO

Chemotherapy induced nausea and vomiting is problematic for many patients undergoing chemotherapy. Multiple-drug treatments have been developed to mitigate chemotherapy induced nausea and vomiting. A patient-controlled infusion of diphenhydramine hydrochloride, lorazepam, and dexamethasone sodium phosphate has been studied in patients who are refractory to first-line therapy. Unfortunately, the physical and chemical compatibility of this three-drug combination is not available in the published literature. Chemical compatibility was evaluated using high-performance liquid chromatography with ultraviolet detection. Visual observation was employed to detect change in color, clarity, or gas evolution. Turbidity and pH measurements were performed in conjunction with visual observation at hours 0, 24, and 48. Results showed that diphenhydramine hydrochloride 4 mg/mL, lorazepam 0.16 mg/mL, and dexamethasone sodium phosphate 0.27 mg/mL in 0.9% sodium chloride stored in polypropylene syringes were compatible, and components retained greater than 95% of their original concentration over 48 hours when stored at room temperature.


Assuntos
Dexametasona/análogos & derivados , Difenidramina/química , Lorazepam/química , Dexametasona/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Polipropilenos , Cloreto de Sódio/química , Seringas
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