RESUMO
SUMMARY: Malignancies in human immunodeficiency virus (HIV) positive individuals have a larger role in morbidity and mortality. Appropriate clinical acumen is required for a clinician to anticipate the occurrence of lymphoma after starting antiretroviral therapy, especially in patients with CD4 <100 cells/mm3. Here is a 30-year-old man with weight loss and appetite, found to be retroviral disease positive status with low CD 4 counts. He was started on antiretroviral treatment, and following that, he developed Hodgkin's lymphoma of mixed cellularity. He is planned for an ABVD regimen and received one cycle of the same without any complications. To our knowledge, we are reporting the first case of an HIV patient with a mixed cellularity form of classical Hodgkin's lymphoma from India.
Assuntos
Infecções por HIV , Doença de Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Masculino , Adulto , Infecções por HIV/tratamento farmacológico , Índia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócito CD4 , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/administração & dosagem , Dacarbazina/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Antirretrovirais/uso terapêutico , Antirretrovirais/efeitos adversosRESUMO
A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Cardiomiopatias , Dacarbazina , Doxorrubicina , Doença de Hodgkin , Síndrome da Leucoencefalopatia Posterior , Vimblastina , Humanos , Doença de Hodgkin/tratamento farmacológico , Feminino , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Doxorrubicina/efeitos adversos , Dacarbazina/efeitos adversos , Bleomicina/efeitos adversos , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adulto , Diagnóstico Diferencial , Antraciclinas/efeitos adversos , Gencitabina , Imageamento por Ressonância MagnéticaRESUMO
Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100â¯%) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Complicações Neoplásicas na Gravidez , Humanos , Doença de Hodgkin/tratamento farmacológico , Gravidez , Feminino , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Vimblastina/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Dacarbazina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Resultado do Tratamento , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Bleomicina/efeitos adversos , Adulto , Doxorrubicina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/administração & dosagem , Resultado da GravidezRESUMO
Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Brentuximab Vedotin , Dacarbazina , Doxorrubicina , Doença de Hodgkin , Tomografia por Emissão de Pósitrons , Vimblastina , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Brentuximab Vedotin/uso terapêutico , Masculino , Feminino , Adulto , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Vimblastina/uso terapêutico , Vimblastina/administração & dosagem , Dacarbazina/uso terapêutico , Dacarbazina/administração & dosagem , Adulto Jovem , Estadiamento de Neoplasias , Idoso , Resultado do Tratamento , SeguimentosRESUMO
INTRODUCTION: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. PURPOSE: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. METHODS: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. RESULTS: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. CONCLUSION: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etoposídeo , Doença de Hodgkin , Prednisona , Procarbazina , Vincristina , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Masculino , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Adulto , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Feminino , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Dacarbazina/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Adolescente , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etoposídeo , Doença de Hodgkin , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prednisona , Procarbazina , Vimblastina , Vincristina , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Adulto , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Pessoa de Meia-Idade , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Feminino , Masculino , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Adulto Jovem , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Intervalo Livre de ProgressãoRESUMO
A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.
Assuntos
Vacinas Anticâncer , Ciclofosfamida , Células Dendríticas , Neoplasias , Medicina de Precisão , Humanos , Células Dendríticas/imunologia , Masculino , Feminino , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/uso terapêutico , Criança , Neoplasias/mortalidade , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Medicina de Precisão/métodos , Terapia Combinada , Pré-Escolar , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Adolescente , Administração Metronômica , Imunoterapia/métodos , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Lactente , Inibidores de Checkpoint Imunológico/uso terapêutico , SeguimentosRESUMO
Classical Hodgkin lymphoma (cHL) is diagnosed in patients ages 60 and older in approximately 20%-25% of cases in Western populations. Outcomes in this subset of patients have historically been poor, with 5-year progression free survival (PFS) and overall survival rates significantly lower than those seen in younger patients. Challenges to overcome include age-related co-morbidities, and prominent and potentially lethal treatment-related toxicity. There have been increased efforts to study the older cHL patient population, including analysis of geriatric assessments and the integration of newer targeted therapies such as brentuximab vedotin (BV) and nivolumab (N) into treatment paradigms. A recent phase 3 clinical trial (S1826, NCT03907488) led by the North American oncology cooperative groups compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (BV-AVD) with nivolumab, doxorubicin, vinblastine, and dacarbazine (N-AVD). At a median follow-up of 1-year, N-AVD improved PFS vs BV-AVD in patients and few immune adverse events were observed. Moreover, in a pre-planned subset analyses of cHL patients ages ≥60 years, the 1-year PFS for N-AVD was 93% (95% CI, 79%-98%) versus 64% (95% CI, 45%-77%) for BV-AVD. In addition, N-AVD was largely better tolerated particularly in older patients, which included markedly less neuropathy, lower treatment discontinuation, and less nonrelapse mortality. As a result, N-AVD is poised to become a standard of care for older, advanced-stage cHL patients who are fit for full-dose anthracycline-based combination therapy. More studies are needed to continue to improve outcomes for older cHL patients, especially unfit and frail populations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doença de Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin/uso terapêutico , Doxorrubicina/uso terapêutico , Doxorrubicina/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Idoso de 80 Anos ou mais , Dacarbazina/uso terapêutico , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Fatores Etários , Vimblastina/uso terapêutico , Vimblastina/efeitos adversos , Ensaios Clínicos Fase III como AssuntoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin , Doença de Hodgkin , Nivolumabe , Humanos , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/terapia , Doença de Hodgkin/patologia , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Criança , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Masculino , Feminino , Antineoplásicos Imunológicos/uso terapêutico , Adolescente , Imunoterapia/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/uso terapêuticoRESUMO
PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.
Assuntos
Administração Metronômica , Fibromatose Agressiva , Metotrexato , Centros de Atenção Terciária , Humanos , Masculino , Feminino , Adulto , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/mortalidade , Fibromatose Agressiva/economia , Índia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Metotrexato/economia , Padrão de Cuidado , Criança , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Tamoxifeno/administração & dosagem , Tamoxifeno/economia , Tamoxifeno/uso terapêutico , Estudos RetrospectivosRESUMO
Vanishing bile duct syndrome is an uncommon condition characterised by the progressive loss and disappearance of bile ducts. It is an acquired form of cholestatic liver disease presenting with hepatic ductopenia (loss of >50% bile ducts in the portal areas). We present a case of vanishing bile duct syndrome as a presentation of Hodgkin's lymphoma who was treated with standard-of-care chemotherapy-doxorubicin, bleomycin, vinblastine and dacarbazine (along with brief administration of rituximab), which led to complete response and normalisation of liver function.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Doença de Hodgkin , Adulto , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças dos Ductos Biliares/diagnóstico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Dacarbazina/administração & dosagem , Doxorrubicina/uso terapêutico , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/diagnóstico , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Síndrome , Vimblastina/uso terapêutico , Vimblastina/administração & dosagemRESUMO
Combination checkpoint inhibitor (CPI) and chemotherapy is an effective and safe treatment strategy for patients with untreated classic Hodgkin lymphoma. Recent studies of programmed cell death protein 1 inhibitors combined with doxorubicin, vinblastine and dacarbazine have demonstrated high overall and complete response rates. This combination has a unique toxicity profile that should be managed appropriately so as not to compromise treatment efficacy. Common toxicities include rash, hepatoxicity, neutropenia and thyroid dysfunction. Here, we present four cases and the management strategies around such toxicities. In addition, we highlight key clinical decision-making around the administration of subsequent doses of CPI and chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Doença de Hodgkin , Inibidores de Checkpoint Imunológico , Humanos , Doença de Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Masculino , Feminino , Adulto , Doxorrubicina/efeitos adversos , Doxorrubicina/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Pessoa de Meia-Idade , Dacarbazina/efeitos adversos , Dacarbazina/administração & dosagem , Neutropenia/induzido quimicamenteRESUMO
OBJECTIVE: To determine whether neoadjuvant gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) before radical cystectomy improves overall survival (OS), progression-free survival (PFS), and pathologic complete response (pCR) for patients with muscle-invasive bladder cancer with secondary analyses of pathological downstaging and toxicity. MATERIALS AND METHODS: This systematic review and meta-analysis identified studies of patients with muscle-invasive bladder cancer treated with neoadjuvant GC compared to ddMVAC from PubMed, Web of Science, and EMBASE. Random-effect models for pooled log-transformed hazard ratios (HR) for OS and PFS and pooled odds ratios for pCR and downstaging were developed using the generic inverse variance method and Mantel-Haenszel method, respectively. RESULTS: Ten studies were identified (4 OS, 2 PFS, and 6 pCR clinical endpoints). Neoadjuvant ddMVAC improved OS (HR 0.71 [95% confidence intervals 0.56; 0.90]), PFS (HR 0.76 [95% confidence intervals 0.60; 0.97]), and pathological downstaging (odds ratio 1.34 [95% confidence interval 1.01; 1.78]) as compared to GC. There was no significant difference between regimens for pCR rates (odds ratio 1.38 [95% confidence interval 0.90; 2.12]). Treatment toxicity was greater with ddMVAC. Limitations result from differences in number of ddMVAC cycles and patient selection between studies. CONCLUSION: Neoadjuvant ddMVAC is associated with improved OS and PFS vs gemcitabine/cisplatin for patients with muscle-invasive bladder cancer before radical cystectomy. Although rates of pathological complete response were not significantly different, pathological downstaging correlated with OS. ddMVAC should be preferred over gemcitabine/cisplatin for patients with muscle-invasive bladder cancer who can tolerate its greater toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/mortalidade , Humanos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gencitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Cistectomia/métodos , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Quimioterapia Adjuvante/métodosRESUMO
Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Fator Estimulador de Colônias de Granulócitos , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Neutropenia Febril/prevenção & controle , Neutropenia Febril/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Neoplasias Urológicas/tratamento farmacológico , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vimblastina/efeitos adversosRESUMO
PURPOSE: Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens. METHODS: After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed. RESULTS: The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months. CONCLUSION: Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Feminino , Criança , Masculino , Neoplasias do Tronco Encefálico/tratamento farmacológico , Pré-Escolar , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adolescente , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Glioma Pontino Intrínseco Difuso/tratamento farmacológico , Temozolomida/uso terapêutico , Temozolomida/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vimblastina/análogos & derivados , Lactente , Resultado do TratamentoRESUMO
The article "The impact of bleomycin deficit on survival in Hodgkin's lymphoma patients: A retrospective study" have presented the experience of AVD chemotherapy regimen in newly diagnosed Hodgkin's lymphoma (HL) in a single center in Brazil. Though being a small retrospective study, results from this study have provided the medical community a real-world data on HL in Brazil. ABVD has remained the standard of care for patients of newly diagnosed HL both in early and advance stages. Newer targeted molecules have also come for use in novel combinations with existing drugs. However, in a situation of temporary scarcity of bleomycin due to lack of supply during 2017 in Brazil led to use of incomplete ABVD regimen without bleomycin, i.e. AVD for HL. However, Soldi et al. utilized the opportunity to retrospectively study if the omission of bleomycin leads to subnormal treatment or unwarranted effects.
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Bleomicina , Doença de Hodgkin , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Bleomicina/uso terapêutico , Bleomicina/administração & dosagem , Humanos , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vimblastina/uso terapêutico , Brasil/epidemiologia , Doxorrubicina/uso terapêutico , Dacarbazina/uso terapêuticoRESUMO
BACKGROUND: This multicenter Phase I study (NCT03585465) evaluated nivolumab in combination with 3 metronomic chemotherapy (MC) regimens in children with refractory/relapsing solid tumors. OBJECTIVES: To evaluate the feasibility and safety of the three regimens METHODS: Patients aged < 18 years were enrolled. Nivolumab was combined with cyclophosphamide and vinblastine (arm A), capecitabine (arm B), or cyclophosphamide, vinblastine and capecitabine (arm C). Arm A and B were allocated sequentially. Arm C opened only if A and B were deemed safe. Dose-limiting toxicities (DLTs) were evaluated over the first two cycles. Patients were evaluable if they received > 2 cycles and > 70% of the planned dose. POPULATION: Sixteen patients were enrolled, 3 in arm A, 6 in arm B, and 7 in arm C. Median age was 11.5 years (range, 5-19). Patients previously received a median of 3.5 (range, 1-4) lines of systemic treatment, 14 patients had surgery and 11 had radiotherapy. RESULTS: Median number of cycles was 2 (1-24), median treatment duration was 56 days (18-714). In arm C, median number of cycles was 4 with median treatment duration of 95 days. No DLT was observed. Grade 3 adverse events (AE) and serious AE were observed in 8 patients (50%) and 1 patient (6%), respectively, over the first 2 cycles. No grade 4 AE occurred. The 6-month PFS and OS were 12% and 44%, respectively, in the whole population. Prolonged stable disease was observed in a high-grade glioma and an atypical teratoid rhabdoid tumor. CONCLUSION: Arm C appears safe. A randomized phase II trial evaluating the addition of nivolumab to the triple MC is ongoing.
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Recidiva Local de Neoplasia , Nivolumabe , Adolescente , Criança , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Ciclofosfamida , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Nivolumabe/uso terapêutico , Vimblastina/uso terapêutico , Pré-EscolarRESUMO
Many chemotherapeutic drugs suffer from multidrug resistance (MDR). Efflux transporters, namely ATP-binding cassettes (ABCs), that pump the drugs out of the cancer cells comprise one major reason behind MDR. Therefore, ABC inhibitors have been under development for ages, but unfortunately, without clinical success. In the present study, an l-type amino acid transporter 1 (LAT1)-utilizing derivative of probenecid (PRB) was developed as a cancer cell-targeted efflux inhibitor for P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and/or several multidrug resistant proteins (MRPs), and its ability to increase vinblastine (VBL) cellular accumulation and apoptosis-inducing effects were explored. The novel amino acid derivative of PRB (2) increased the VBL exposure in triple-negative human breast cancer cells (MDA-MB-231) and human glioma cells (U-87MG) by 10-68 -times and 2-5-times, respectively, but not in estrogen receptor-positive human breast cancer cells (MCF-7). However, the combination therapy had greater cytotoxic effects in MCF-7 compared to MDA-MB-231 cells due to the increased oxidative stress recorded in MCF-7 cells. The metabolomic study also revealed that compound 2, together with VBL, decreased the transport of those amino acids essential for the biosynthesis of endogenous anti-oxidant glutathione (GSH). Moreover, the metabolic differences between the outcomes of the studied breast cancer cell lines were explained by the distinct expression profiles of solute carriers (SLCs) that can be concomitantly inhibited. Therefore, attacking several SLCs simultaneously to change the nutrient environment of cancer cells can serve as an adjuvant therapy to other chemotherapeutics, offering an alternative to ABC inhibitors.
Assuntos
Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Vimblastina/farmacologia , Vimblastina/metabolismo , Vimblastina/uso terapêutico , Probenecid/farmacologia , Probenecid/uso terapêutico , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Neoplasias/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Apoptose , Estresse Oxidativo , Aminoácidos/metabolismo , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular TumoralRESUMO
PURPOSE: We aimed to assess the prognostic value of baseline tumor burden and dissemination parameters extracted from 18 F-FDG PET/CT in patients with early or advanced Hodgkin lymphoma (HL) treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated BEACOPP (increased bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone). PATIENTS AND METHODS: Patients aged ≥18 years with classical Hodgkin lymphoma were retrospectively included. Progression-free survival (PFS) analysis of dichotomized clinicobiological and PET/CT parameters (SUV max , TMTV, TLG, D max , and D bulk ) was performed. Optimal cutoff values for quantitative metrics were defined as the values maximizing the Youden index from receiver operating characteristic analysis. PFS rates were estimated with Kaplan-Meier curves, and the log-rank test was used to assess statistical significance. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: With a median age of 32 years, 166 patients were enrolled. A total of 111 patients had ABVD or ABVD-like treatment with or without radiotherapy and 55 patients with escalated BEACOPP treatment. The median follow-up was 55 months. Only International Prognostic Score (IPS >1), TMTV >107 cm 3 , and TLG >1628 were found to be significant prognostic factors for PFS on univariate analysis. Multivariate analysis revealed that IPS and TLG were independently prognostic and, combined, identified 4 risk groups ( P < 0.001): low (low TLG and low IPS; 4-year PFS, 95%), intermediate-low (high IPS and low TLG; 4-year PFS, 79%), intermediate-high (low IPS and high TLG; 4-year PFS, 78%), and high (high TLG and high IPS; 4-year PFS, 71%). CONCLUSIONS: Combining baseline TLG with IPS could improve PFS prediction.