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1.
Future Oncol ; 19(23): 1577-1591, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37334673

RESUMO

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).


In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Linfócitos T CD8-Positivos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Fase III como Assunto
2.
Am J Case Rep ; 24: e938982, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36810727

RESUMO

BACKGROUND Patients with advanced stage ovarian cancer typically have vague non-specific abdominal symptoms related to pelvic tumor, metastasis, and ascites. When these patients present with more acute abdominal pain, appendicitis is rarely considered. Acute appendicitis due to metastatic ovarian cancer has been sparsely documented in the medical literature; only twice, to our knowledge. CASE REPORT A 61-year-old woman with a 3-week history of abdominal pain, shortness of breath, and bloating was diagnosed with ovarian cancer after computed tomography (CT) demonstrated a large pelvic cystic and solid mass. Five weeks later she underwent an omental biopsy to determine cell type and potential upstaging of the ovarian cancer to stage IV, as other aggressive cancers such as breast cancer can also involve the pelvis/omentum. Seven hours after her biopsy, she presented with increasing abdominal pain. Post-biopsy complications such as hemorrhage or bowel perforation were initially suspected to be the cause of her abdominal pain. However, CT demonstrated ruptured appendicitis. The patient underwent an appendectomy and histopathologic examination of the specimen revealed infiltration by low-grade ovarian serous carcinoma. CONCLUSIONS Given the low incidence of spontaneous acute appendicitis in this patient's age group, and the lack of any other clinical, surgical, or histopathological evidence to suggest another cause, metastatic disease was ruled to be the likely source of her acute appendicitis. Providers should be aware of appendicitis in a broad differential diagnosis and have a low threshold for ordering abdominal pelvis CT when advanced stage ovarian cancer patients present with acute abdominal pain.


Assuntos
Abdome Agudo , Apendicite , Neoplasias Ovarianas , Feminino , Humanos , Pessoa de Meia-Idade , Apendicite/diagnóstico , Apendicectomia/efeitos adversos , Dor Abdominal/etiologia , Ascite/complicações
3.
J Clin Oncol ; 41(4): 914-930, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36469839

RESUMO

PURPOSE: To provide guidance on the use of opioids to manage pain from cancer or cancer treatment in adults. METHODS: A systematic review of the literature identified systematic reviews and randomized controlled trials of the efficacy and safety of opioid analgesics in people with cancer, approaches to opioid initiation and titration, and the prevention and management of opioid adverse events. PubMed and the Cochrane Library were searched from January 1, 2010, to February 17, 2022. American Society of Clinical Oncology convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 31 systematic reviews and 16 randomized controlled trials. Opioids have primarily been evaluated in patients with moderate-to-severe cancer pain, and they effectively reduce pain in this population, with well-characterized adverse effects. Evidence was limited for several of the questions of interest, and the Expert Panel relied on consensus for these recommendations or noted that no recommendation could be made at this time. RECOMMENDATIONS: Opioids should be offered to patients with moderate-to-severe pain related to cancer or active cancer treatment unless contraindicated. Opioids should be initiated PRN (as needed) at the lowest possible dose to achieve acceptable analgesia and patient goals, with early assessment and frequent titration. For patients with a substance use disorder, clinicians should collaborate with a palliative care, pain, and/or substance use disorder specialist to determine the optimal approach to pain management. Opioid adverse effects should be monitored, and strategies are provided for prevention and management.Additional information is available at www.asco.org/supportive-care-guidelines.


Assuntos
Dor do Câncer , Neoplasias , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adulto , Analgésicos Opioides/efeitos adversos , Dor/tratamento farmacológico , Dor/etiologia , Manejo da Dor , Dor do Câncer/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico
4.
Am J Case Rep ; 23: e932649, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038319

RESUMO

BACKGROUND Diamond-Blackfan anemia (DBA) is a rare genetic disorder associated with macrocytic anemia and reticulocytopenia, with patients usually transfusion-dependent in the first years of life. The disease inheritance is predominantly autosomal dominant, but varying presentations have been described owing to incomplete penetrance and widely variable expression. De novo mutations have been reported in about 55% of cases. This pediatric disease is commonly characterized by malformation of the extremities as well as craniofacial abnormalities and cardiac and urogenital defects. There have been reported cases of adult-onset DBA diagnosed through genetic testing. Although these adult-onset cases can vary in presentation, characteristic malformations are present in nearly half of patients. Treatment protocols include corticosteroids, blood transfusions, iron chelation, and bone marrow transplant. New investigational therapies are being evaluated. Roughly one-fourth of patients achieve remission and are able to maintain a stable hemoglobin level without intervention. CASE REPORT A 35-year-old woman with spina bifida and resultant paraplegia presented with new-onset transfusion-dependent hypoplastic anemia. Following an extensive evaluation, a RPL11 gene variant was found, confirming the diagnosis of DBA. CONCLUSIONS DBA should be considered in young adult patients with severe, transfusion-dependent, aregenerative anemia without definitive cause. Evaluation for nonclassical DBA should be considered and excluded.


Assuntos
Anemia de Diamond-Blackfan , Anemia , Adulto , Anemia de Diamond-Blackfan/diagnóstico , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/terapia , Transfusão de Sangue , Criança , Feminino , Testes Genéticos , Humanos , Mutação , Adulto Jovem
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