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1.
BMC Neurol ; 21(1): 424, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34724914

RESUMO

OBJECTIVE: Glioblastoma multiforme (GBM) is the most common primary malignant central nervous system (CNS) tumor. The Stupp regimen is the standard treatment, although the optimal number of temozolomide (TMZ) treatment cycles remains controversial. We compared the effects of standard 6 cycles versus > 6 cycles of TMZ chemotherapy post-surgery with concurrent chemoradiotherapy on primary GBM patient survival. PATIENTS AND METHODS: We performed a single center retrospective study of GBM patients that underwent total resection, concurrent chemoradiotherapy, and at least 6 cycles of adjuvant TMZ chemotherapy from June 2011 to August 2018. Patients were divided into 2 groups based on adjuvant TMZ treatment plan: Group A(n = 27): standard 6-cycle adjuvant TMZ therapy and Group B(n = 26): > 6 cycles of adjuvant TMZ therapy. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Continuous variables were analyzed by ANOVA, and the Kaplan-Meier method was used to evaluate PFS and OS. Univariate and multivariate COX analyses determined correlation between survival rates and covariates. We used The Mini Mental State Examination (MMSE) and Karnofsky Performance Status (KPS) to assess patients' neurocognitive function and quality of life. RESULTS: After follow-up, median PFS was 15 months in in Group A (95%CI 9.5-20.5) and 20.1 months in Group B (95%CI 15.9-24.4). Group A median OS was 19.4 months (95%CI 15.5-23.2), compared to 25.6 months in Group B (95%CI 20.4-30.8). The 2-year survival rate of Groups A and B was 36% was 66%, respectively (P = 0.02). and 5-year survival was 7% in both. Multivariate COX regression analysis showed association between patient PFS and long-period adjuvant chemotherapy, but not OS. There were no significant difference in disability or quality of life during treatment with Stupp protocol, but differences in MMSE and KPS were in favour of the Groups B after year 1 of the treatment (P < 0.05). CONCLUSIONS: Long-term adjuvant TMZ chemotherapy was beneficial for PFS and 2-year survival rate in GBM patients, and improved their quality of life contemporarily. But OS was not significantly improved.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Quimioterapia Adjuvante , Dacarbazina/uso terapêutico , Glioblastoma/tratamento farmacológico , Humanos , Qualidade de Vida , Estudos Retrospectivos , Temozolomida/uso terapêutico
2.
Rinsho Ketsueki ; 62(10): 1505-1509, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732624

RESUMO

A 66-year-old woman was being treated with methotrexate and etanercept for rheumatoid arthritis (RA). Because her RA symptoms worsened, her medication was changed to tocilizumab (TCZ), and her symptoms improved. However, one year and six months later, she was referred to our hospital because of fever, cervical and para-aortic lymphadenopathy, and massive lesions of the liver/spleen. She was diagnosed with clinical stage IVB mixed cellularity classical Hodgkin lymphoma (cHL) on the basis of right cervical lymph node biopsy. Immunohistochemically, Hodgkin cells were positive for CD20, CD30, PAX-5, LMP-1, PD-L1, and EBER and were negative for CD5, CD15, and EBNA2. Her fever and lymphadenopathy did not improve after the discontinuation of TCZ. Therefore, she was administered ABVd therapy and achieved complete remission (CR) after six cycles of ABVd therapy. She was found to be alive and in CR on regular follow up till February 2021. To the best of our knowledge, there are limited reports of immunodeficiency-related lymphoproliferative disorders associated with TCZ in literature, and our case may be a valuable report on the association of TCZ with the development of cHL in patients with RA.


Assuntos
Artrite Reumatoide , Doença de Hodgkin , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , Vimblastina/uso terapêutico
3.
Medicina (Kaunas) ; 57(10)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34684063

RESUMO

Background and objectives: Hodgkin lymphoma (HL) is characterized by the presence of malignant Reed Sternberg cells. Although the current curability rate in patients with HL has increased, up to 30% of those in the advanced stages and 5% to 10% of those in limited stages of the disease, relapse. According to the studies, the relapse risk in HL decreases after 2 years. The purpose of this study is to evaluate the relapse risk and event free survival (EFS) in patients with HL treated with Doxorubicin, Bleomycin, Vinblastine and Dacarbazine (ABVD), or treated with Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone (BEACOPP) regimens. Material and methods: In an observational, consecutive-case scenario, 71 patients (median age 32 years; range 16 to 80 years) diagnosed within a 4-year timeframe were enrolled; all patients were treated according to standards of care. The average follow-up duration was 26 months. Results: The risk of relapse, in patients older than 40 years, decreased after 1 year, OR = 0.707 (95% CI 0.506 to 0.988), and 2 years, OR = 0.771 (95% CI 0.459 to 1.295), respectively. Patients in the advanced stages had a higher International Prognostic Score (IPS) (score ≥ 4). The overall survival at 2 years was 57.74% and the disease-specific survival at 2 years was 71.83%. Regardless, the chemotherapy regimen and the EFS time, advanced stage, high IPS and bulky disease were still associated with an increased relapse risk in patients with HL. Conclusions: The use of ABVD chemotherapy regimen followed by 2 years EFS was associated with a reduced relapse risk.


Assuntos
Doença de Hodgkin , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Recidiva , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
4.
N Engl J Med ; 385(13): 1196-1206, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34551229

RESUMO

BACKGROUND: Uveal melanoma is a disease that is distinct from cutaneous melanoma, with a low tumor mutational burden and a 1-year overall survival of approximately 50% in patients with metastatic uveal melanoma. Data showing a proven overall survival benefit with a systemic treatment are lacking. Tebentafusp is a bispecific protein consisting of an affinity-enhanced T-cell receptor fused to an anti-CD3 effector that can redirect T cells to target glycoprotein 100-positive cells. METHODS: In this open-label, phase 3 trial, we randomly assigned previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with single-agent pembrolizumab, ipilimumab, or dacarbazine (control group), stratified according to the lactate dehydrogenase level. The primary end point was overall survival. RESULTS: A total of 378 patients were randomly assigned to either the tebentafusp group (252 patients) or the control group (126 patients). Overall survival at 1 year was 73% in the tebentafusp group and 59% in the control group (hazard ratio for death, 0.51; 95% confidence interval [CI], 0.37 to 0.71; P<0.001) in the intention-to-treat population. Progression-free survival was also significantly higher in the tebentafusp group than in the control group (31% vs. 19% at 6 months; hazard ratio for disease progression or death, 0.73; 95% CI, 0.58 to 0.94; P = 0.01). The most common treatment-related adverse events in the tebentafusp group were cytokine-mediated events (due to T-cell activation) and skin-related events (due to glycoprotein 100-positive melanocytes), including rash (83%), pyrexia (76%), and pruritus (69%). These adverse events decreased in incidence and severity after the first three or four doses and infrequently led to discontinuation of the trial treatment (2%). No treatment-related deaths were reported. CONCLUSIONS: Treatment with tebentafusp resulted in longer overall survival than the control therapy among previously untreated patients with metastatic uveal melanoma. (Funded by Immunocore; ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).


Assuntos
Antineoplásicos/uso terapêutico , Melanoma/secundário , Neoplasias Uveais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Síndrome da Liberação de Citocina/induzido quimicamente , Dacarbazina/uso terapêutico , Exantema/induzido quimicamente , Feminino , Humanos , Ipilimumab/uso terapêutico , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Análise de Sobrevida , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/mortalidade
5.
Rinsho Ketsueki ; 62(8): 1102-1111, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497197

RESUMO

Four cycles of ABVD followed by 30 Gy IFRT (ISRT) is a standard regimen, as an initial treatment, for patients with early-stage classical Hodgkin lymphoma (cHL), whereas 2 cycles of ABVD followed by 20 Gy IFRT (ISRT) is an alternative regimen for those with favorable early-stage cHL. For patients with unfavorable early-stage cHL including bulky disease, local radiotherapy can be safely omitted if negative findings on interim PET are obtained after 2 cycles of escalated BEACOPP plus 2 cycles of ABVD. ABVD (6/8 cycles) or brentuximab vedotin (BV) with concurrent AVD (6 cycles) is a standard regimen for patients with advanced-stage cHL. For elderly cHL patients (60 years of age or older) and multiple comorbidities, the risk of treatment-related adverse events is higher, which can potentially lead to poor outcomes. BV with sequential AVD therapy, which is a unique combination strategy, has been developed for elderly cHL patients. The combination of anti-PD-1 antibodies with AVD therapies is currently being evaluated in some clinical trials. This review includes current evidence that primarily focuses on randomized clinical trials for newly diagnosed adult cHL patients and management points in clinical practice for those patients.


Assuntos
Doença de Hodgkin , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Estadiamento de Neoplasias , Vimblastina/uso terapêutico
6.
J Thromb Haemost ; 19(10): 2630-2631, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558780
8.
J Egypt Natl Canc Inst ; 33(1): 21, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34396456

RESUMO

BACKGROUND: Hodgkin lymphoma (HL) is lymphoid neoplasm usually affecting lymphatic system; it accounts 3.6% of cancers in Saudi Arabia. Modern treatment protocols had shown particular success rates in overall-survival (OS) and event-free-survival (EFS). In our study, we reviewed the medical records of 80 pediatric and young adolescent patients diagnosed HL from January 2006 to July 2020, treated at tertiary care hospital in Riyadh, Saudi Arabia. Demographic, clinical, and pathological data were explored. First line therapy was ABVD, COG, COPP, R-CHOP, or radiotherapy alone in 53/80 (66.4%), 24/80 (30%), 1/80 (1.2%), 1/80 (1.2%), or 1/80 (1.2%) patients; respectively. Response assessment was done by CT + / - PET scan after first 2 cycles then every 2 cycle and end of therapy. Another assessment was done if any clinical suspicion of recurrence. RESULTS: Median age 11 (range 3-16) years. Males to females 1.3:1. Seventy-two out of eighty (90%) patients showed first complete remission (CR1) and maintained remission for median 40 (range 7-136) months. Eight out of eighty (10%) patients showed refractory disease. Nineteen patients received salvage therapy (ICE or ESHAP/brentuximab vedotin or gemcitabine/brentuximab vedotin), 14/19 (73.7%) had 2nd complete remission (CR2) for median time 24 (ranged 9-78) months, while 5/19 (26.3%) did not show any response. Five-year OS and EFS were 95% and 75%. Two patients had 2ry malignant neoplasms, one had AML and died, the other had malignant fibrous histocytoma and still alive. None of our patients had fertility problem. Also, they did not experience chronic pulmonary or cardiotoxicity. Classic Hodgkin's lymphoma: nodular sclerosis subtype was more prominent (55%) than mixed cellularity subtype (22.5%), which is similar to several European and US studies, lymphocyte rich (11.25%) and lymphocyte depleted (0%), while nodular lymphocyte predominant Hodgkin's lymphoma (11.25%). CONCLUSIONS: Our study provided unique descriptive study of childhood HL, in Saudi Arabia, with valuable insight into the long-term outcome and late toxicity. Our results are comparable to other studies in the Middle East and European countries.


Assuntos
Doença de Hodgkin , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Criança , Pré-Escolar , Dacarbazina/uso terapêutico , Doxorrubicina , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/terapia , Humanos , Masculino , Recidiva Local de Neoplasia , Arábia Saudita/epidemiologia , Centros de Atenção Terciária , Resultado do Tratamento , Vimblastina/uso terapêutico
9.
Crit Rev Oncol Hematol ; 166: 103457, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34428555

RESUMO

Malignant tumors in young patients present a significant therapeutic challenge for physicians, partially due to their rarity and a relative lack of data, at least compared to adult tumors. As a result, there is an urgent need to explore new possible therapeutic regimens, either by introducing novel agents or by exploring combinations of existing agents. Vincristine, Temozolomide and Irinotecan are chemotherapeutic drugs which have emerged over the last six decades as monotherapy or as part of therapeutic regimens in various solid tumors. Combining these agents can yield strong synergistic effects, as suggested by preclinical data and results from clinical trials. Furthermore, adding novel molecules, such as anti-VEGF factor Bevacizumab to the aforementioned regimens, has shown efficacy in a limited number of trials, which are thoroughly analyzed throughout this review. Data presented throughout this paper suggest that VIT(b) regimen should be further explored in solid tumors in pediatric and adolescent patients.


Assuntos
Neoplasias Encefálicas , Neoplasias , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/uso terapêutico , Criança , Dacarbazina/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Neoplasias/tratamento farmacológico , Temozolomida/uso terapêutico , Vincristina
10.
Hum Reprod ; 36(10): 2743-2752, 2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34417822

RESUMO

STUDY QUESTION: What is the influence of age and chemotherapy regimen on the longitudinal blood anti-Müllerian hormone (AMH) variations in a large series of adolescents and young adult (AYA) (15-24 years old) and non-AYA (25-35 years old) lymphoma patients? SUMMARY ANSWER: In case of alkylating regimen treatment, there was a deep and sustained follicular depletion in AYA as well as non-AYA patients; however in both groups, the ovarian toxicity was extremely low in cases of non-alkylating treatments. WHAT IS KNOWN ALREADY: AMH is now well-recognised to be a real-time indicator of ovarian follicular depletion and recovery in women treated by chemotherapy. Its longitudinal variations may discriminate between highly and minimally toxic protocols regarding ovarian function. It has been shown, in different cancer types, that age, type of chemotherapy regimen and pre-treatment AMH levels are the main predictors of ovarian recovery. Large studies on longitudinal AMH variations under chemotherapy in lymphoma patients are few but can provide the opportunity to assess the degree of follicle loss at a young age. STUDY DESIGN, SIZE, DURATION: This prospective cohort study was conducted in the Fertility Observatory of the Lille University Hospital. Data were collected between 2007 and 2016. Non-Hodgkin or Hodgkin lymphoma patients (n = 122) between 15 and 35 years old were prospectively recruited before commencing chemotherapy. Patients were treated either by a non-alkylating protocol (ABVD group; n = 67) or by an alkylating regimen (alkylating group; n = 55). PARTICIPANTS/MATERIALS, SETTING, METHODS: Serial AMH measurements were performed at baseline (AMH0), 15 days after the start of chemotherapy (AMH1), 15 days before the last chemotherapy cycle (AMH2), and at time 3, 6, 9, 12, 18 and 24 months from the end of chemotherapy. The whole study population was divided into two groups according to age: AYA (15-24; n = 65) and non-AYA (25-35; n = 57). All patients received a once monthly GnRH agonist injection during the whole treatment period. A linear mixed model was used to account for the repeated measures of single patients. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, non-AYA patients had higher BMI and lower AMH levels than AYA patients. All AYA and non-AYA patients having received ABVD protocols had regular cycles at 12 months of follow-up. In case of alkylating regimens, amenorrhoea was more frequent in non-AYA patients than in AYA patients at 12 months (37% vs 4%, P = 0.011) and at 24 months (24% vs 4%, P = 0.045). We distinguished a similar depletion phase from AMH0 to AMH2 between ABVD and alkylating groups but significantly different recovery phases from AMH2 to AMH + 24 months. AMH recovery was fast and complete in case of ABVD protocols whatever the age: AMH reached pre-treatment values as soon as the 6th month of follow-up in the AYA group (mean (95% CI) in log AMH M0 vs M6: 3.07 (2.86 to 3.27) vs 3.05 (2.78 to 3.31), P = 1.00) and in the non-AYA group (mean (95% CI) in log AMH M0 vs M6: 2.73 (2.40 to 3.05) vs 2.47 (2.21 to 2.74), P = 1.00). In contrast, no patients from the alkylating group returned to pre-treatment AMH values whatever the age of patients (AYA or non-AYA). Moreover, none of the AMH values post-chemotherapy in the non-AYA group were significantly different from AMH2. Conversely in the AYA group, AMH levels from 6 months (mean (95% CI) in log AMH: 1.79 (1.47 to 2.11), P < 0.001) to 24 months (mean (95% CI) in log AMH: 2.16 (1.80 to 2.52), P ≤ 0.001) were significantly higher than AMH2 (mean (95% CI) in log AMH: 1.13 (0.89 to 1.38)). Considering the whole study population (AYA and non-AYA), pre-treatment AMH levels influenced the pattern of the AMH variation both in alkylating and ABVD protocols (interaction P-value = 0.005 and 0.043, respectively). Likewise, age was significantly associated with the pattern of the recovery phase but only in the alkylating group (interaction P-value =0.001). BMI had no influence on the AMH recovery phase whatever the protocol (interaction P-value = 0.98 in alkylating group, 0.72 in ABVD group). LIMITATIONS, REASONS FOR CAUTION: There was a large disparity in subtypes of protocols in the alkylating group. The average duration of chemotherapy for patients treated with alkylating protocols was longer than that for patients treated with ABVD. WIDER IMPLICATIONS OF THE FINDINGS: These results make it possible to develop strategies for fertility preservation according to age and type of protocol in a large series of young lymphoma patients. In addition, it was confirmed that young age does not protect against ovarian damage caused by alkylating agents. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Agence Régionale de Santé Hauts de France and Agence Onco Hauts-de-France who provided finances for AMH dosages (n° DOS/SDES/AR/FIR/2019/282). There are no competing interests. TRIAL REGISTRATION NUMBER: DC-2008-642 and CNIL DEC2015-112.


Assuntos
Preservação da Fertilidade , Doença de Hodgkin , Adolescente , Adulto , Hormônio Antimülleriano , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/uso terapêutico , Aconselhamento , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Estudos Longitudinais , Estudos Prospectivos , Vimblastina/uso terapêutico , Adulto Jovem
11.
Blood Adv ; 5(18): 3647-3655, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34438445

RESUMO

Radiotherapy (RT) is typically incorporated into the treatment of limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), although it remains unknown whether chemotherapy alone may be suitable in select patients. We evaluated outcomes of limited-stage NLPHL at BC Cancer on the basis of era-specific guidelines: routine RT era, 1995 to 2005 (n = 36), combined modality with 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by RT or RT alone; positron emission tomography (PET) era, after 2005 (n = 63), ABVD alone (4 cycles) if the PET scan after the second cycle of ABVD (PET2) is negative, or treatment is changed to RT if PET2 is positive. Median age of patients was 38 years (range, 16-82 years), 73% were male, and 43% had stage II. With a median follow-up of 10.5 years for all patients, 5-year progression-free survival (PFS) was 93% and was 97% for overall survival (OS), with no difference by treatment era (PFS, P = .13; OS, P = .35). For the 49 patients who had a PET2 scan, 86% were PET negative and 14% were PET positive by Deauville criteria with 5-year PFS rates of 92% and 80% (P = .70), respectively. This is the largest study of a PET-adapted approach in NLPHL and supports that ABVD alone may be a viable option in select patients with a negative PET2 scan, with consideration of acute and long-term toxicities.


Assuntos
Doença de Hodgkin , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Vimblastina/uso terapêutico , Adulto Jovem
12.
Blood Adv ; 5(18): 3623-3632, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34448831

RESUMO

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale-Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.


Assuntos
Doença de Hodgkin , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Vimblastina/uso terapêutico
14.
CNS Oncol ; 10(3): CNS76, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34378977

RESUMO

Aim: Investigate real-world outcomes and healthcare utilization of patients with glioblastoma multiforme (GBM) related to O6-methylguanine DNA methyltransferase (MGMT) promoter testing and methylation. Patients & methods: US Oncology Network data were analyzed for patients receiving first-line (1L) treatment for GBM. Results: Most patients received 1L radiation with temozolomide. Unadjusted median overall survival (OS) was higher in tested versus untested (median:18.1 vs 11.8 months) and in methylated versus unmethylated (median: 25.5 vs 12.4 months). Untested status, unmethylated MGMT and older age were associated with reduced OS and longer 1L treatment with increased OS. Similar findings were observed for progression-free survival. Utilization was similar between cohorts. Conclusion: In community oncology practices, MGMT methylation and testing were predictive of better survival in GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/terapia , Humanos , Estudos Retrospectivos , Proteínas Supressoras de Tumor/genética
15.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204367

RESUMO

The constitutive expression or overactivation of cyclooxygenase (COX) and lipoxygenase (LOX) enzymes results in aberrant metabolism of arachidonic acid and poor prognosis in melanoma. Our aim is to compare the in vitro effects of selective COX-1 (acetylsalicylic acid), COX-2 (meloxicam), 5-LOX (MK-886 and AA-861), 12-LOX (baicalein) and 15-LOX (PD-146176) inhibition in terms of proliferation (SRB assay), mitochondrial viability (MTT assay), caspase 3-7 activity (chemiluminescent assay), 2D antimigratory (scratch assay) and synthesis of eicosanoids (EIA) in the B16F10 cell line (single treatments). We also explore their combinatorial pharmacological space with dacarbazine and temozolomide (median effect method). Overall, our results with single treatments show a superior cytotoxic efficacy of selective LOX inhibitors over selective COX inhibitors against B16F10 cells. PD-146176 caused the strongest antiproliferation effect which was accompanied by cell cycle arrest in G1 phase and an >50-fold increase in caspases 3/7 activity. When the selected inhibitors are combined with the antineoplastic drugs, only meloxicam provides clear synergy, with LOX inhibitors mostly antagonizing. These apparent contradictions between single and combination treatments, together with some paradoxical effects observed in the biosynthesis of eicosanoids after FLAP inhibition in short term incubations, warrant further mechanistical in vitro and in vivo scrutiny.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Lipoxigenase/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidores de Ciclo-Oxigenase/química , Dacarbazina/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Inibidores de Lipoxigenase/química , Melanoma Experimental , Camundongos , Estrutura Molecular , Temozolomida/farmacologia
16.
Ann Hematol ; 100(10): 2547-2556, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34327561

RESUMO

We investigated the feasibility and activity of an intensified dose-dense ABVD (dd-ABVD) regimen in patients with early-stage unfavorable Hodgkin lymphoma (HL). This prospective, multicenter, phase II study enrolled 96 patients with newly diagnosed, unfavorable stage I or II classical HL. The patients received four cycles of dd-ABVD followed by radiotherapy. Interim PET (PET-2) was mandatory after two courses. Primary endpoints were the evaluation of dd-ABVD feasibility and activity (incidence of PET-2 negativity). The feasibility endpoint was achieved with 48/52 (92.3%) patients receiving > 85% of the programmed dose. The mean dose intensity in the overall patient population (n = 96) was 93.7%, and the median duration of dd-ABVD was 85 days (range, 14-115) versus an expected duration of 84 days. PET-2 was available for 92/96 (95.8%) patients, of whom 79 were PET-2 negative (85.9%). In total, 90 (93.8%) patients showed complete response at the end of treatment. With a follow-up of 80.9 months (3.3-103.2), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 84 months, PFS and OS rates were 88.4% and 95.7%, respectively. No evidence for a difference in PFS or OS was observed for PET-2-negative and PET-2-positive patients. Infections were documented in 8.3% and febrile neutropenia in 6.2% of cases. Four patients died: one had alveolitis at cycle 3, one death was unrelated to treatment, and two died from a secondary cancer. dd-ABVD is feasible and demonstrates activity in early-stage unfavorable HL. The predictive role of PET-2 positivity in early-stage unfavorable HL remains controversial. The study was registered in the EudraCT (reference number, 2011-003,191-36) and the ClinicalTrials.gov (reference number, NCT02247869) databases.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/epidemiologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Adulto Jovem
17.
Curr Oncol ; 28(4): 2399-2408, 2021 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206775

RESUMO

(1) Background: Studies in elderly patients over the age of 65 with glioblastoma have shown survival benefits of short-course radiation therapy with concurrent and adjuvant temozolomide, making it the standard of care adopted at Juravinski Cancer Center. Our study retrospectively examines patients with GBM aged ≥ 70 at the JCC treated with short-course radiation alone compared to those treated with short-course radiation and concurrent and adjuvant TMZ, to determine if there is a difference in outcomes based on performance status. (2) Methods: A retrospective chart review was conducted at JCC using patients diagnosed with GBM in 2014-2017 (treated with the old protocol of short-course RT alone) versus those diagnosed in 2017-2019 (treated with the new protocol of short-course radiation and TMZ). Patient demographics, treatments, outcomes, and baseline KPS were analyzed. (3) Results: No clear benefit and more neurologic decline post treatment were seen in patients with borderline performance status and subtotal resection who underwent concurrent treatment with temozolomide and radiation. The addition of temozolomide was most helpful in patients with good performance status and a gross total resection. Variable outcomes were seen in patients with mixed traits. (4) Conclusions: This study suggests that performance status and extent of resection are significant determinants of patient response to treatment. In the case of elderly patients with borderline performance status and GTR or those with good performance status and STR, also described as "mixed traits", it may be beneficial to pursue single modality treatment, ideally based on MGMT promoter methylation status as opposed to bimodality treatment in order to maintain the best QOL.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/uso terapêutico , Glioblastoma/tratamento farmacológico , Humanos , Qualidade de Vida , Estudos Retrospectivos , Temozolomida/uso terapêutico
20.
J Control Release ; 337: 296-305, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34298055

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Despite the gold standard treatment combining surgical resection, radiation and adjuvant plus concomitant chemotherapy with the alkylating agent temozolomide (TMZ), the prognosis remains poor (5-year survival rate < 10%). Over the last three decades, a vast array of drug delivery systems (DDS) have been developed for the local treatment of GBM, with the majority of the characterization being undertaken in pre-clinical models. We aimed to gain an overview of the potential efficacy of such local delivery systems in comparison to the systemic drug administration. METHODS: In this paper, a systematic search of Pubmed, Web of Science, and Scopus was performed using pre-determined search terms. Studies were assessed for eligibility based on specific inclusion and exclusion criteria. A total of fifteen publications were included for analysis of local vs systemic group median survival, tumor volume and adverse events, with five brought forward for a meta-analysis. RESULTS: The majority of studies showed local delivery to be more efficacious than systemic administration, regardless of the drug, animal model, type of DDS used, or duration of the study. The meta-analysis also showed that the mean difference between median survival ratios was statistically significantly in favor of local delivery. CONCLUSION: Preclinical evidence shows that there is a firm rationale for further developing DDS for local therapeutic delivery to GBM and other brain cancers.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Preparações Farmacêuticas , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/uso terapêutico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Humanos
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