RESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Brentuximab Vedotina , Dacarbazina , Doxorrubicina , Enfermedad de Hodgkin , Tomografía de Emisión de Positrones , Vinblastina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Brentuximab Vedotina/uso terapéutico , Masculino , Femenino , Adulto , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Vinblastina/uso terapéutico , Vinblastina/administración & dosificación , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Adulto Joven , Estadificación de Neoplasias , Anciano , Resultado del Tratamiento , Estudios de SeguimientoRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Complicaciones Neoplásicas del Embarazo , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Embarazo , Femenino , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vinblastina/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Resultado del Tratamiento , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Bleomicina/efectos adversos , Adulto , Doxorrubicina/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Resultado del EmbarazoRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Ciclofosfamida , Dacarbazina , Doxorrubicina , Etopósido , Enfermedad de Hodgkin , Prednisona , Procarbazina , Vincristina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéutico , Vincristina/administración & dosificación , Masculino , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Procarbazina/uso terapéutico , Adulto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Femenino , Etopósido/administración & dosificación , Etopósido/efectos adversos , Etopósido/uso terapéutico , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Dacarbazina/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/uso terapéutico , Persona de Mediana Edad , Adulto Joven , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Adolescente , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
The authors Lanke and Relander describe a patient with classical Hodgkin lymphoma (cHL) stage IIA, who had pain at alcohol consumption as the only symptom at diagnosis. The patient was treated with 4 cycles of ABVD chemotherapy and proton therapy 29.75 Gy (RBE). Apart from FDG-PET/CT the course of the disease was followed with serum-TARC. The case illustrates the value of knowing also rare symptoms at the general practice, the usefulness of TARC as a tumour marker in cHL, and the use of proton therapy in order to further reduce late radiotherapy side effects.
Asunto(s)
Consumo de Bebidas Alcohólicas , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Consumo de Bebidas Alcohólicas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Terapia de Protones/efectos adversos , Bleomicina/efectos adversos , Bleomicina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones , DacarbazinaRESUMEN
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.
Asunto(s)
Vacunas contra el Cáncer , Ciclofosfamida , Células Dendríticas , Neoplasias , Medicina de Precisión , Humanos , Células Dendríticas/inmunología , Masculino , Femenino , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/uso terapéutico , Niño , Neoplasias/mortalidad , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Medicina de Precisión/métodos , Terapia Combinada , Preescolar , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Adolescente , Administración Metronómica , Inmunoterapia/métodos , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Lactante , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios de SeguimientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotina , Enfermedad de Hodgkin , Nivolumab , Humanos , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/patología , Nivolumab/uso terapéutico , Nivolumab/administración & dosificación , Niño , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Masculino , Femenino , Antineoplásicos Inmunológicos/uso terapéutico , Adolescente , Inmunoterapia/métodos , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/uso terapéuticoRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Enfermedad de Hodgkin , Adulto , Femenino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Conductos Biliares/diagnóstico , Bleomicina/administración & dosificación , Bleomicina/uso terapéutico , Dacarbazina/uso terapéutico , Dacarbazina/administración & dosificación , Doxorrubicina/uso terapéutico , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/diagnóstico , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Síndrome , Vinblastina/uso terapéutico , Vinblastina/administración & dosificaciónRESUMEN
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.
Asunto(s)
Administración Metronómica , Fibromatosis Agresiva , Metotrexato , Centros de Atención Terciaria , Humanos , Masculino , Femenino , Adulto , Fibromatosis Agresiva/tratamiento farmacológico , Fibromatosis Agresiva/mortalidad , Fibromatosis Agresiva/economía , India , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Adolescente , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Metotrexato/economía , Nivel de Atención , Niño , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Tamoxifeno/administración & dosificación , Tamoxifeno/economía , Tamoxifeno/uso terapéutico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To compare the efficacy and safety of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with gemcitabine-based regimens for neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) patients treated in Japan. METHODS: Data for MIBC patients who received NAC-dd-MVAC followed by a radical cystectomy from June 2019 to May 2023 performed at our hospital were analyzed. For comparisons, data for MIBC patients who received NAC gemcitabine and cisplatin (GC) or gemcitabine and carboplatin (GCarbo) therapy between January 2010 and March 2019 were also obtained. Rates of ypT1N0 or less, progression-free survival (PFS), overall survival (OS), and NAC adverse effects were compared between the GC/GCarbo and dd-MVAC regimens. RESULTS: Results for 32 patients who received dd-MVAC and 30 who received GC/GCarbo NAC therapy were analyzed. ypT1N0 or less was noted in 40.7% of the dd-MVAC and 40.0% of the GC/GCarbo groups, while ypT0N0 rates were 25% and 10%, respectively, with no statistical differences noted. However, Kaplan-Meier analysis of the total cohort demonstrated that dd-MVAC was associated with significantly better PFS and OS rates than GG/GCarbo (hazard ratios: 0.33, p = 0.0237, and 0.23, p = 0.0127, respectively). Propensity-matched models also showed similar results for both PFS and OS. Adverse effects of dd-MVAC were acceptable and the incidence of hematologic toxicity was lower as compared with GC/GCarbo therapy. CONCLUSION: The present study is the first to show that dd-MVAC as NAC can provide better survival as compared with a gemcitabine-based regimen for patients with MIBC treated in Japan.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Cistectomía , Desoxicitidina , Doxorrubicina , Gemcitabina , Metotrexato , Terapia Neoadyuvante , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Vinblastina , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/mortalidad , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Femenino , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/efectos adversos , Anciano , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Persona de Mediana Edad , Japón/epidemiología , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Supervivencia sin ProgresiónRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina , Enfermedad de Hodgkin , Inhibidores de Puntos de Control Inmunológico , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Masculino , Femenino , Adulto , Doxorrubicina/efectos adversos , Doxorrubicina/administración & dosificación , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Persona de Mediana Edad , Dacarbazina/efectos adversos , Dacarbazina/administración & dosificación , Neutropenia/inducido químicamenteRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Terapia Neoadyuvante , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/mortalidad , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Terapia Neoadyuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Cistectomía/métodos , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Quimioterapia Adyuvante/métodosRESUMEN
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).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Factor Estimulante de Colonias de Granulocitos , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Neutropenia Febril/prevención & control , Neutropenia Febril/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Neoplasias Urológicas/tratamiento farmacológico , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Vinblastina/efectos adversosRESUMEN
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.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Femenino , Niño , Masculino , Neoplasias del Tronco Encefálico/tratamiento farmacológico , Preescolar , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Glioma Pontino Intrínseco Difuso/tratamiento farmacológico , Temozolomida/uso terapéutico , Temozolomida/administración & dosificación , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , Vinblastina/análogos & derivados , Lactante , Resultado del TratamientoRESUMEN
Background and purpose To predict treatment-related cardiovascular disease (CVD) and second cancer 30-yea. absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. Material and methods This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 20162019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and doseresponse relationships. Results Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 46 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.223.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. Conclusion For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects (AU)
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Neoplasias del Mediastino/etiología , Neoplasias del Mediastino/radioterapia , Neoplasias Primarias Secundarias , Radioterapia de Intensidad Modulada , Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Dosificación Radioterapéutica , Vinblastina/administración & dosificaciónRESUMEN
BACKGROUND: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available. METHODS: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed. RESULTS: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up. CONCLUSIONS: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
Asunto(s)
Antineoplásicos Inmunológicos , Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotina , Enfermedad de Hodgkin , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Brentuximab Vedotina/administración & dosificación , Brentuximab Vedotina/efectos adversos , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estudios de Seguimiento , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversosRESUMEN
Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de Supervivencia , Insuficiencia del Tratamiento , Vinblastina/administración & dosificación , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin , Leucemia Linfocítica Crónica de Células B , Neoplasias Primarias Secundarias , Adulto , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/patología , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. METHODS AND ANALYSIS: Oncodistinct 004 - AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. ETHICS AND DISSEMINATION: The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03674424).
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Humanos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Neoplasias de la Vejiga Urinaria/patología , Vinblastina/administración & dosificación , Vinblastina/uso terapéutico , GemcitabinaRESUMEN
Langerhans cell histiocytosis (LCH) is a rare systemic disease caused by proliferation of mature histiocytes; its association to histiocyto fibroma is rarely reported. It rarely affects adults. We report a case of systemic LCH, in an adult patient with osteolytic lesion causing a fistula between the left nasal cavity and hard palate, involving the bone, lung, lymph node and associated to multiple histiocyto fibroma. The patient was operating for a fistula, and he was treated by chemotherapy and corticosteroids. Langerhans´ cell histiocytosis is a rare case, especially in adult patient. The diagnosis was based on histological and immunohistochemical analyses. This patient was treated by steroids and chemotherapy.
Asunto(s)
Histiocitosis de Células de Langerhans/diagnóstico , Cavidad Nasal/anomalías , Fístula Oral/diagnóstico , Corticoesteroides/administración & dosificación , Adulto , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Humanos , Masculino , Cavidad Nasal/cirugía , Fístula Oral/etiología , Fístula Oral/cirugía , Vinblastina/administración & dosificaciónRESUMEN
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.