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1.
ACS Appl Mater Interfaces ; 14(12): 14025-14032, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35302731

RESUMO

Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2 infections. The antiviral efficacy of hypericin is largely determined by its affinity toward viral components and by the number of active molecules loaded on single viruses. Here we use an experimental approach to follow the interaction of hypericin with SARS-CoV-2, and we evaluate its antiviral efficacy, both in the dark and upon photoactivation. Binding to viral particles is directly visualized with fluorescence microscopy, and a strong affinity for the viral particles, most likely for the viral envelope, is measured spectroscopically. The loading of a maximum of approximately 30 molecules per viral particle is estimated, despite with marked heterogeneity among particles. Because of this interaction, nanomolar concentrations of photoactivated hypericin substantially reduce virus infectivity on Vero E6 cells, but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug.


Assuntos
Antivirais , COVID-19 , Animais , Antracenos , Antivirais/química , COVID-19/tratamento farmacológico , Chlorocebus aethiops , Perileno/análogos & derivados , SARS-CoV-2 , Células Vero
2.
Tumori ; : 3008916221083702, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35341397

RESUMO

OBJECTIVE: To describe in non-small cell lung cancer (NSCLC) the impact of visceral pleural invasion (VPI) and of tumor sizing assessed at computed tomography (CT) on the agreement between clinical-radiological and pathological T staging and its prognostic value. METHODS: Patients affected by NSCLC treated by surgery in the period from January 2017 to September 2020 were retrospectively evaluated. Exclusion criteria were: (1) baseline CT not performed in our hospital; (2) failure of software segmentation at CT of the primary lesion. Clinical-radiological T (cT) was assessed at baseline CT, evaluating in particular T size by semi-automatic tool and VPI (cVPI) visually. Pathological T (pT) and VPI (pVPI) were recorded by pathological report and obtained after formalin-fixation and eventual elastic stain on surgical specimen. The agreement between cT and pT was evaluated by calculating the weighted kappa by Cohen (κw); the association between progression free survival (PFS) with both cT and pT was assessed by the Cox regression analysis. RESULTS: The study included 84 NSCLC in 82 patients (median age 71 years, IQR 63-76 years; females 22/82, 27%). The agreement between cT and pT was poor (κw 0.302, 95%CI 0.158-0.447). The main causes of disagreement were CT oversizing (21%) and false positive cVPI (29%). A significant association was found between PFS and pT2-T3 (HR 2.75, 95%CI 1.21-6.25, p=0.015) but not with cT2-T3 (not retained in the model). CONCLUSIONS: False positive cVPI and oversizing at CT are causes of disagreement between cT and pT in around one-third of resected NSCLC. PFS was significantly associated with pT but not with cT.

3.
Biomol Concepts ; 13(1): 126-147, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35304984

RESUMO

Photodynamic therapy (PDT) is a clinically approved procedure that can exert a curative action against malignant cells. The treatment implies the administration of a photoactive molecular species that, upon absorption of visible or near infrared light, sensitizes the formation of reactive oxygen species. These species are cytotoxic and lead to tumor cell death, damage vasculature, and induce inflammation. Clinical investigations demonstrated that PDT is curative and does not compromise other treatment options. One of the major limitations of the original method was the low selectivity of the photoactive compounds for malignant over healthy tissues. The development of conjugates with antibodies has endowed photosensitizing molecules with targeting capability, so that the compounds are delivered with unprecedented precision to the site of action. Given their fluorescence emission capability, these supramolecular species are intrinsically theranostic agents.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio
4.
Gastric Cancer ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35352176

RESUMO

BACKGROUND: EOX (epirubicin, oxaliplatin, and capecitabine) is one of the standard regimens for metastatic or locally advanced gastric cancer (GC). A new combination based on fractional docetaxel (low-TOX) has been developed in an attempt to increase the efficacy of EOX and reduce the heavy toxicity of classical docetaxel regimens. METHODS: Overall, 169 previously untreated GC patients were randomized between EOX (arm A) and low-TOX (arm B). The primary endpoint was progression-free survival (PFS), while secondary ones were overall survival (OS), overall response rate (ORR), disease control rate (DCR), and tolerability. The study was designed to detect a 35% (80% power at a two-sided 5% significance level) PFS increase with low-TOX and an interim analysis for futility was planned after the first 127 events. RESULTS: At the cut-off date of interim analysis, median PFS was 6.3 months [95% confidence interval (CI) 5.0-8.1] in arm A vs 6.3 months (95% CI 5.0-7.8) in arm B, without statistical difference. OS was comparable in the two arms: 12.4 in arm A (95% CI 9.1-19.2) vs 11.5 months in arm B (95% CI 8.6-15.0). ORR was 33% and 24%, while DCR was 68% and 67%, respectively. Treatment modification (91% vs 78%, P = 0.017) and number of patients with CTC grade ≥ 3 adverse events (42 vs 35) were higher in arm B. CONCLUSIONS: A triplet regimen based on the fractional dose of docetaxel achieves no improvement over EOX which remains a potential standard treatment in many patients with inoperable, locally advanced or metastatic GC.

5.
Biomol Concepts ; 13(1): 175-182, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35355498

RESUMO

The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors. Fe-protoporphyrin IX was replaced by the photosensitizing compound Zn-protoporphyrin IX. Taking advantage of the fluorescence emission by Zn-protoporphyrin IX, we show that the construct can bind prostate cancer cells where the VPAC receptors are expressed.


Assuntos
Antibacterianos , Antibacterianos/química , Humanos , Espécies Reativas de Oxigênio , Proteínas Recombinantes
6.
Vaccines (Basel) ; 10(2)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35214623

RESUMO

Patients with cancer have a high risk of intubation, intensive care unit admission, or death from the coronavirus disease (COVID-19); age and comorbidities are additional risk factors. Vaccination is effective against COVID-19; however, patients with cancer have been excluded from pivotal clinical trials for COVID-19 vaccines. Data on COVID-19 vaccination in cancer patients who are older are lacking. This observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or mRNA1273 vaccine in older patients (age ≥ 70 years) with solid tumors or with hematological malignances who are undergoing active anticancer treatment or whose treatment has been terminated within 6 months of vaccination. The control group was composed of healthy volunteers that were age-matched with the patient group. The primary endpoint was the seropositivity rate, and the secondary endpoints were safety, the factors influencing seroconversion, the IgG titers of patients versus healthy volunteers, and post-vaccine COVID-19 infection between 20 March 2021 and 14 July 2021. At our Institution (Oncology and Hematology Department, Hospital of Piacenza, North Italy), 443 patients with cancer underwent a program for COVID-19 vaccination; 115 (25.95%) were older than 70 (range 71-86 years) and form the basis of this study. All 115 patients accepted the vaccination. There were 64 female patients (55.65%), 94 patients (81.74%) with solid tumors, and 21 patients (18.26%) with hematological malignances. The primary endpoint of seropositivity was observed in 75 patients (65.22%)-70.21% in patients with solid tumors and 42.86% in patients with hematological malignances-versus in 100% of patients in the control group. Of the secondary endpoints, no grade 3-4 side effects and no COVID-19 infections were reported. The factor influencing seroconversion was the type of cancer. The patients' median IgG titers were significantly lower than in the control groups. The COVID-19 vaccines BNT162b2 and mRNA1273 were effective and safe among older patients with cancer when administered in real-world conditions.

7.
Support Care Cancer ; 30(4): 3225-3231, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34977981

RESUMO

PURPOSE: Little is known about the real impact of the COVID-19 outbreak on the qualitative and quantitative fall-out on the management of cancer patients. Our objective was to provide evidence of the effects of SARS-COV-2 on the management of cancer patients in the real world. METHODS: In a general hospital in a district in Italy with high prevalence of COVID-19 during the first wave, we retrospectively analyzed the data of oncologic activity, namely new cancer diagnosis, types of treatment (intravenous or by mouth), clinical research studies, and drug utilization, and compared the findings with those of 2019, before the pandemic. The data have been summarized in boxplot figures for median and interquartile range. RESULTS: In 2020, a significant reduction in new cancer diagnosis was demonstrated when compared with 2019, with 17.4% fewer cancer diagnoses, 84.5% fewer patients enrolled in clinical trials, a 10.6% reduction in intravenous antitumor treatment, and a 42.7% increase in oral anticancer treatment. CONCLUSION: Our data indicate a significant reduction in cancer diagnosis, antitumor venous treatment, and patients enrolled in clinical research studies in 2020 compared with 2019, although there was a significant increase in oral treatment. These data suggest that the COVID-19 pandemic had a deep impact on the real-world management of cancer patients in a district of Italy with a high prevalence of COVID-19.


Assuntos
COVID-19 , Pandemias , Ensaios Clínicos como Assunto , Hospitais Gerais , Humanos , Itália/epidemiologia , Prevalência , Estudos Retrospectivos , SARS-CoV-2
8.
Recenti Prog Med ; 112(12): 785-791, 2021 12.
Artigo em Italiano | MEDLINE | ID: mdl-34924573

RESUMO

INTRODUCTION: The natural history of cancer has radically changed in the last decade. The burden of travel from patient's residence to health care providers is an important issue that can influence access to diagnosis and treatment of cancer; however this issue is quite neglect by the medical community and by the national health system. In addition, community care in the oncology field is actually debated. METHODS: In the district of Piacenza an innovative model to deliver onco-hematologic treatment near the residence of patients was initiated some years ago. The oncologic and hematologic treatments are delivered by specialized nurses under supervision of medical oncologists or hematologists at the 3 community hospital and at 1 house of health in the district of Piacenza. We conducted a retrospective study involving 1,339 cancer patients (CPs) managed and treated near their residence, CPs were on active medical treatment at the oncology and hematology department Azienda sanitaria (ASL) of Piacenza (North Italy). The electronic data base of the antiblastic drug unit (UFA) of the ASL Piacenza, provided: the number of patients treated each year, number of treatments and the accesses to the territorial medical structure each year. The kms saved to reach the nearest territorial structures instead of the oncologic unit of the city hospital, were registered and recorded. RESULTS: During a 4 years period, from January 2017 to December 2020, 1,339 CPs were treated near their residence, 278 in the year 2017, 347 in 2018, 354 in 2019 and 360 in 2020. The total accesses for treatment in 4 years were 10,003: 2,214 in the year 2017, 2,652 in 2018, 2,524 in 2019 and 2,613 in 2020. The mean distance saved for each patient was 937 kms in the year 2017, 891 in 2018, 879 in 2019, 920 in 2020, totally a mean of 3,627 kms in the 4 years. DISCUSSION AND CONCLUSION: We believe that the results of our retrospective study highlight the possibility of treating cancer patients in territorial structures near their residence, with advantages for patients themselves, their caregivers and for the entire community.


Assuntos
Neoplasias , Cuidadores , Humanos , Itália , Neoplasias/terapia , Estudos Retrospectivos , Viagem
10.
Cureus ; 13(10): e18418, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34733594

RESUMO

Mortality from coronavirus disease 2019 (COVID-19) is higher among patients with cancer. Vaccination represents a cornerstone in overcoming the disease, and vaccine safety needs to be closely assessed. This article discusses two cases of herpes zoster (HZ) following the administration of the BNT162b2 mRNA vaccine in patients who are long-term survivors of breast disease. HZ developed 24 days and two days after the second dose of the vaccine in women aged 81 and 61, respectively. These two patients were breast cancer operated respectively nine and 16 years before; interestingly HZ developed in the same site of previous surgical resection. The patients did not show lymphocytopenia or other signs of immunosuppression and were treated with acyclovir, resulting in the complete resolution of HZ. To our knowledge, these two patients are the first described cases of HZ reactivation following COVID-19 vaccination in cancer survivors.

12.
Nutrients ; 13(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34684483

RESUMO

Breast cancer (BC) is a major public health concern and substantial research has shown that adhering to a healthy dietary pattern, such as the Mediterranean Diet (MD), may prevent the onset of cancer and BC relapses. This study aims at specifically investigating the association of MD with circulating dietary-related biomarkers in a cohort of BC survivors. Eighty patients (mean age of 54.9 ± 10.6) with a histologically confirmed diagnosis of BC who had not received any pharmacological or radiotherapy treatment for at least two months were enrolled. Fasting serum lipid-soluble vitamins (retinol, tocopherol), plant pigments (ß-carotene, lutein + zeaxanthin, cryptoxanthin, lycopene), inflammatory and oxidative stress markers (ceruloplasmin; haptoglobin; paraoxonases; reactive oxygen molecule; thiol groups, Ferric reducing antioxidant power), and cardiometabolic parameters (body mass index (BMI); glucose; insulin; HOMA-IR; total cholesterol; LDL-cholesterol; HDL-cholesterol; triglycerides) were analyzed. Adherence to the MD was assessed through the Mediterranean Diet Score (MDS) questionnaire. Fasting blood samples were collected for the evaluation of selected biomarkers. MDS resulted positively correlated with ß-carotene (r 0.331; p < 0.01) and lycopene (r 0.274; p < 0.05) and negatively with retinol (r -0.346; p < 0.05). Among the investigated inflammatory biomarkers, MDS was only correlated with antioxidant capacity (r 0.256; p < 0.05), while none of the investigated cardiometabolic parameters were significantly correlated with this index. The strong significant correlation between ß-carotene and MDS encourages us to consider this pro-vitamin as a putative biomarker to take into account for evaluating the adherence to the MD.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Sobreviventes de Câncer , Dieta Mediterrânea , Mediadores da Inflamação/sangue , Lipídeos/química , Micronutrientes/sangue , Carotenoides/sangue , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Pessoa de Meia-Idade , Solubilidade , Vitaminas/sangue
13.
Eur J Cancer ; 157: 441-449, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34601285

RESUMO

INTRODUCTION: Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. METHODS: An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2-6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. RESULTS: Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28-86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3-4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile.


Assuntos
Vacinas contra COVID-19/imunologia , Neoplasias/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Feminino , Humanos , Imunogenicidade da Vacina/imunologia , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias/virologia , Pandemias/prevenção & controle , Estudos Prospectivos , SARS-CoV-2/imunologia , Vacinação/métodos
14.
Tohoku J Exp Med ; 255(1): 61-69, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34588347

RESUMO

North Italy emerged as an epicenter of COVID-19 in the Western world. The majority of studies of patients with COVID-19 have focused on hospitalized patients, and data on early outpatient treatment are limited. This research retrospectively examines consecutive symptomatic adults who did not present to a hospital but who experience laboratory confirmed (nasopharyngeal swabs) or probable COVID-19 infection. From March 12 to April 12, 2020, 124 consecutive patients with laboratory-confirmed COVID-19 infection (84%) or with epidemiologically linked exposure to a person with confirmed infection (16%) were managed at home. The diagnosis of pneumonia was made with a portable ultrasound. COVID-19 treatment was based on low-dose hydroxychloroquine with or without darunavir/cobicistat or azithromycin and enoxaparine for bedridden patients. The patients were monitored by telemedicine. The primary endpoints were clinical improvement or hospitalization, and the secondary endpoints were mortality at day 30 and at day 60. Forty-seven (37.9%) patients had mild COVID-19 infection, 44 (35.5%) had moderate COVID-19 infection, and 33 (26.6%) had severe COVID-19 infection. Four patients (3.2%) were hospitalized and there were no deaths at day 30 and at day 60. Only mild side effects were reported. Early home treatment of COVID-19 patients resulted in a low hospitalization rate with no deaths, with the limitations of the small sample size and that it was conducted within a single geographic area. We believe that this model may be easily reproduced in both cities and rural areas around the world to treat COVID-19 infection.


Assuntos
COVID-19/epidemiologia , Surtos de Doenças , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Azitromicina/uso terapêutico , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Teste para COVID-19 , Cobicistat/uso terapêutico , Darunavir/uso terapêutico , Combinação de Medicamentos , Feminino , Serviços de Assistência Domiciliar , Hospitalização , Humanos , Hidroxicloroquina/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Telemedicina , Adulto Jovem
15.
Vaccines (Basel) ; 9(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34579285

RESUMO

Patients with cancer are among the most vulnerable groups of the COVID-19 pandemic, whereas vaccinations can represent a cornerstone in overcoming the pandemic itself. However, cancer patients were excluded from clinical trials for COVID-19 vaccinations, and thus the data on the immunogenicity and safety of COVID-19 vaccines in cancer patients are limited. In this systematic review, we assessed the seroconversion rate and the safety of COVID-19 vaccinations in cancer patients. We searched a bibliographic database up until 31 July 2021. Utilizing inclusion criteria, six studies were selected and analyzed for this meta-analysis. This included 621 cancer patients and 256 controls. Results show that patients with solid tumors show adequate antibody responses (>90%), though the antibody titers were significantly lower than those of healthy controls. Similarly, a significantly lower rate of seroconversion was registered in patients with hematologic malignances. The vaccines showed a good safety profile; no grade 3-4 adverse events were registered. This review demonstrates generally high immunogenicity from COVID-19 vaccines in patients with cancer, with better results for solid tumors than hematological malignances, and with a good safety profile.

16.
Clin Lymphoma Myeloma Leuk ; 21(12): 831-840, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34373225

RESUMO

INTRODUCTION/BACKGROUND: The treatment of acute lymphoblastic leukemia (ALL) in patients older than 70 is extremely challenging with dismal outcome. Allogeneic stem cell transplantation (alloHCT) has seen many advancements in the last decades showing benefits in younger ALL patients, but this treatment modality is decreasingly used with increasing age due to high treatment-related mortality. PATIENTS AND METHODS: We identified 84 ALL patients 70 to 84 years old allografted In 2002 to 2019 from a matched related (23%), unrelated (58%), haploidentical (17%), or cord blood (2%) donor at EBMT participating centers with a median follow-up of 23 months. RESULTS: The 2-year relapse incidence (RI) and non-relapse mortality were 37% and 28%, respectively, and 2-year leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 35%, 39% and 23%, respectively. The strongest predictor of outcome was disease status at transplant whereby patients in first complete remission (CR1) had >50% 2-year OS, reflected in multivariate analysis (MVA) with significant improvement in RI, LFS, and GRFS (HR 0.23, 0.49, and 0.54, respectively). Furthermore, karnofsky score ≥90 reflective of good functional status positively influenced non-relapse mortality in both univariate and MVA (HR 0.37), and interestingly, donor CMV positivity appeared to negatively affect RI, LFS and OS in univariate analysis and RI in MVA (HR 2.87). CONCLUSION: Our data suggest that alloHCT is an option for elderly ALL patients, particularly those carefully selected and transplanted in CR1 especially if failed or without access to novel non-chemotherapy-based approaches.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Idoso de 80 Anos ou mais , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo
17.
Oncologist ; 26(10): e1854-e1861, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34101934

RESUMO

BACKGROUND: To reduce the overall exposure to dexamethasone (DEX) in patients receiving cisplatin-based chemotherapy, we evaluated the noninferiority of DEX on day 1, with or without low-dose DEX on days 2 and 3, combined with an oral fixed-dose combination of netupitant and palonosetron (NEPA), compared with the guideline-consistent use of 4-day DEX. PATIENTS AND METHODS: In this open-label, multicenter study, chemotherapy-naïve patients undergoing high-dose cisplatin (≥70 mg/m2 ), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either (a) no further DEX (DEX1), (b) oral DEX (4 mg daily) on days 2-3 (DEX3), or (c) DEX (4 mg twice daily) on days 2-4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5-day overall phase. The noninferiority margin was set at -15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea). RESULTS: Two-hundred twenty-eight patients, 76 in each arm, were assessable. Noninferiority was met for both DEX-sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% confidence interval, -12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups. CONCLUSION: A simplified regimen of NEPA plus single-dose DEX offers comparable chemotherapy-induced nausea and vomiting prevention throughout 5 days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting of cisplatin-based chemotherapy. IMPLICATIONS FOR PRACTICE: Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy-induced emesis. Although generally considered safe, even short-term DEX use is associated with various side effects, and some evidence suggests that concurrent steroids may reduce the efficacy of immunotherapies. This study demonstrates comparable antiemetic control during the 5 days post-chemotherapy with a simplified regimen of netupitant/palonosetron plus single-dose DEX versus the standard 4-day DEX reference treatment in high-dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to appropriately use in patients where caution with corticosteroid use is advised.


Assuntos
Antieméticos , Cisplatino , Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Dexametasona , Humanos , Palonossetrom/uso terapêutico , Piridinas , Quinuclidinas , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle
18.
Clin Case Rep ; 9(6): e04013, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34136224

RESUMO

Patients with hematological cancer are at major risk of developing infectious complication. The prevention and treatment of COVID-19 in these patients is challenging. This experience, with the limitation of a small number of patients, highlights that early treatment of COVID-19 can overcome the infection, also in hematological patients.

19.
Eur J Cancer ; 153: 133-141, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34153715

RESUMO

AIM: The Cher-LOB randomised phase II study showed that the combination of lapatinib-trastuzumab plus chemotherapy increases pathologic complete response (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. Here, we report the post hoc survival analysis as per treatment arm, pCR and biomarkers. METHODS: The Cher-LOB study randomised 121 patients with human epidermal growth factor receptor 2-positive, stage II-IIIA breast cancer. A specific protocol to collect recurrence-free survival (RFS) and overall survival (OS) data was designed. Tumour-infiltrating lymphocytes (TILs) and PAM50-intrinsic subtyping were evaluated at baseline. RESULTS: At 9-year median follow-up, a trend towards RFS improvement with lapatinib-trastuzumab over trastuzumab was observed (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.18-1.05). Combining treatment arms, pCR was significantly associated with both RFS (HR 0.12, 95% CI 0.03-0.49) and OS (HR 0.12, 95% CI 0.03-0.49). TILs were significantly associated with RFS (HR = 0.978 for each 1% increment). Luminal-A subtype was a significant and independent predictor of improved RFS as compared with other PAM50-based intrinsic subtypes at the multivariate analysis including the most relevant clinicopathologic variables (HR 0.29, 95% CI 0.09-0.94, p = 0.040). CONCLUSIONS: Cher-LOB trial survival analysis confirmed the prognostic role of pCR and TILs and showed a signal for a better outcome with lapatinib-trastuzumab over trastuzumab. TRIAL REGISTRATION: NCT00429299.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Lapatinib/uso terapêutico , Terapia Neoadjuvante/métodos , Trastuzumab/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/mortalidade , Feminino , Humanos , Lapatinib/farmacologia , Pessoa de Meia-Idade , Análise de Sobrevida , Trastuzumab/farmacologia
20.
Cureus ; 13(3): e14201, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33948397

RESUMO

Atheroembolic renal disease (AERD) is a life-threatening illness. Coronavirus disease 2019 (COVID-19) has a high mortality rate in older patients with comorbidities. We report the case of severe-type COVID-19 in an 82-year-old female with AERD. She was treated with hydroxychloroquine-based therapy and overcame COVID-19. To our knowledge, this is the first report of a patient with AERD and COVID-19 pneumonia who overcame the infection and remains alive and well nine months following infection.

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