RESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bleomicina , Cardiomiopatías , Dacarbazina , Doxorrubicina , Enfermedad de Hodgkin , Síndrome de Leucoencefalopatía Posterior , Vinblastina , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Femenino , Síndrome de Leucoencefalopatía Posterior/inducido químicamente , Síndrome de Leucoencefalopatía Posterior/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/diagnóstico , Doxorrubicina/efectos adversos , Dacarbazina/efectos adversos , Bleomicina/efectos adversos , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Adulto , Diagnóstico Diferencial , Antraciclinas/efectos adversos , Gemcitabina , Imagen por Resonancia MagnéticaRESUMEN
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
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
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: Hodgkin's lymphoma is currently treated with a chemotherapy protocol consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine. Due to Brazil facing a bleomycin shortage in 2017, and this drug's high toxicity, this retrospective study evaluates the effect that the absence of bleomycin had on treatment response and overall survival of Hodgkin's lymphoma patients. METHODS: The medical records of 126 HL patients treated between 2007 and 2021 were reviewed and their data collected, followed by grouping into ABVD and AVD groups according to bleomycin use. Data concerning the patient's characteristics, cancer type, and treatment plan were analyzed with proportion tests, Kaplan-Meier curves. univariate Cox regression, and χ2 tests. RESULTS: No discernible differences were found in this study between the overall survival and recurrence rate of patients treated with bleomycin compared to those without. Additionally, there was an increased risk of death in each subsequent cycle of chemotherapy of the complete ABVD protocol, demonstrating a risk of toxicity. Among the variables analyzed, hypertension and the presence of B symptoms were also associated with an increased risk of death, while the use of radiotherapy significantly improved survival. CONCLUSION: The results of this study suggest that bleomycin did not impact the outcome of Hodgkin's lymphoma treatment. Moreover, the increased risk of death associated with its toxicity during each cycle of treatment raises concerns about its role as an essential component of the gold standard for Hodgkin's lymphoma treatment. Therefore, further research and consideration are needed to reassess the use of bleomycin in Hodgkin's lymphoma treatment protocols.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/patología , Bleomicina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Doxorrubicina/efectos adversos , Vinblastina/efectos adversos , Dacarbazina/efectos adversosRESUMEN
The primary analysis of the GHSG HD16 trial indicated a significant loss of tumor control with PET-guided omission of radiotherapy (RT) in patients with early-stage favorable Hodgkin lymphoma (HL). This analysis reports long-term outcomes. Overall, 1150 patients aged 18-75 years with newly diagnosed early-stage favorable HL were randomized between standard combined-modality treatment (CMT) (2x ABVD followed by PET/CT [PET-2] and 20 Gy involved-field RT) and PET-2-guided treatment omitting RT in case of PET-2 negativity (Deauville score [DS] < 3). The study aimed at excluding inferiority of PET-2-guided treatment and assessing the prognostic impact of PET-2 in patients receiving CMT. At a median follow-up of 64 months, PET-2-negative patients had a 5-year progression-free survival (PFS) of 94.2% after CMT (n = 328) and 86.7% after ABVD alone (n = 300; HR = 2.05 [1.20-3.51]; p = 0.0072). 5-year OS was 98.3% and 98.8%, respectively (p = 0.14); 4/12 documented deaths were caused by second primary malignancies and only one by HL. Among patients assigned to CMT, 5-year PFS was better in PET-2-negative (n = 353; 94.0%) than in PET-2-positive patients (n = 340; 90.3%; p = 0.012). The difference was more pronounced when using DS4 as cut-off (DS 1-3: n = 571; 94.0% vs. DS ≥ 4: n = 122; 83.6%; p < 0.0001). Taken together, CMT should be considered standard treatment for early-stage favorable HL irrespective of the PET-2-result.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Seguimiento , Dacarbazina/efectos adversos , Vinblastina/efectos adversos , Bleomicina , Doxorrubicina , Estadificación de NeoplasiasRESUMEN
ABSTRACT: Older patients with classical Hodgkin lymphoma (cHL) require more effective and less toxic therapies than younger patients. In this multicenter, prospective, phase 2 study, we investigated a new firstline therapy regimen comprising 6 cycles of prednisone (40 mg/m2, days 1-5), vinblastine (6 mg/m2, day 1), doxorubicin (40 mg/m2, day 1), and bendamustine (120 mg/m2, day 1) (PVAB regimen) every 21 days for patients with newly diagnosed cHL aged ≥61 years with an advanced Ann Arbor stage. A Mini Nutritional Assessment score ≥17 was the cutoff value for patients aged ≥70 years. The primary end point was the complete metabolic response (CMR) rate after 6 cycles. The median age of the 89 included patients was 68 years (range, 61-88 years), with 35 patients (39%) aged ≥70 years. Seventy-eight patients (88%) completed the 6 cycles. The toxicity rate was acceptable, with a 20% rate of related serious adverse events. CMR was achieved by 69 patients (77.5%; 95% confidence interval [CI], 67-86). After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%) from HL (n = 11), toxicity during treatment (n = 4), secondary cancers (n = 6), or other causes (n = 3). The 4-year progression-free survival (PFS) and overall survival rates were 50% and 69%, respectively. Multivariate analysis showed that liver involvement (P = .001), lymphopenia (P = .001), CRP (P = .0005), and comedications (P = .003) were independently associated with PFS. The PVAB regimen yielded a high CMR rate with acceptable toxicity. Over long-term follow-up, survival end points were influenced by unrelated lymphoma events. This trial was registered at www.clinicaltrials.gov as #NCT02414568 and at EudraCT as 2014-001002-17.
Asunto(s)
Enfermedad de Hodgkin , Humanos , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Enfermedad de Hodgkin/patología , Vinblastina/efectos adversos , Prednisona/efectos adversos , Clorhidrato de Bendamustina/efectos adversos , Estudios Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/efectos adversos , Ciclofosfamida , VincristinaRESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.3 years. For all patients, the 7-year progression-free survival (PFS) and overall survival (OS) are 78.2% (95% CI, 75.6 to 80.5) and 91.6% (95% CI, 89.7 to 93.2), respectively. The 1.3% difference in 3-year PFS (95% CI, -3.0 to 4.7) between ABVD and doxorubicin, vinblastine, and dacarbazine (AVD) now falls within the predefined noninferiority margin. Among 172 patients with positive iPET, the 7-year PFS was 65.9% (95% CI, 58.1 to 72.6) and the 7-year OS was 83.2% (95% CI, 76.2 to 88.3). The cumulative incidence of second malignancies at 7 years was 5.5% (95% CI, 4.0 to 7.5) for those receiving ABVD/AVD and 2.5% (95% CI, 0.8 to 7.7) for those escalated to BEACOPP. With extended follow-up, these results confirm noninferiority of treatment de-escalation after a negative iPET. Escalation with BEACOPP for iPET-positive patients is effective and safe, with no increase in second malignancies.
Asunto(s)
Enfermedad de Hodgkin , Neoplasias Primarias Secundarias , Adulto , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Ciclofosfamida/uso terapéutico , Dacarbazina/efectos adversos , Doxorrubicina/efectos adversos , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Neoplasias Primarias Secundarias/tratamiento farmacológico , Prednisona/uso terapéutico , Vinblastina/efectos adversos , Vincristina/efectos adversosRESUMEN
INTRODUCTION: MVAC (Methotrexate, Vinblastine, Adriamycin, and Cisplatin) neoadjuvant chemotherapy a standard treatment for invasive bladder cancer is associated with mainly haematological toxicities. Randomized clinical trials remain a gold standard for treatment outcomes and efficacy assessment. Patients enrolled in clinical trials are selected and tend to benefit from a stricter follow-up unlike everyday clinical practice patients. Conversely, real-life observational studies better define the effectiveness of treatments in clinical routine practice. The aim of this study is to analyse the impact of clinical trial monitoring on MVAC-related toxicities. MATERIAL AND METHODS: Patients with an infiltrative localized bladder cancer treated by MVAC neoadjuvant chemotherapy between 2013 and 2019 were enrolled, and divided into 2 groups: patients included in a clinical trial namely "VESPER study" during their treatment and patients treated in clinical routine practice. RESULTS: Out of 59 patients were enrolled in this retrospective study, 13 patients were included in a clinical trial. Clinical characteristics were similar between the 2 groups. Comorbidities were more frequent in the nonclinical trial group (NCTG). Completed 6 cures treatment proportion was higher in the clinical trial group (CTG) (69.2% vs. 50%). Yet, in this group, patients had more doses reduction (38.5% vs. 19.6%). The proportion of complete pathologic response was higher in patients enrolled in clinical trial (53.8% vs. 39.1%). Statistically, the expected stricter monitoring due to clinical trial enrolment had no impact on the complete pathologic response and clinically relevant toxicities. DISCUSSION: When compared to conventional clinical practice, clinical trial enrolment induced no significant difference on the pathologic complete response or toxicity rate. Further large prospective studies are needed to confirm these data.
Asunto(s)
Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Humanos , Estudios Retrospectivos , Gemcitabina , Desoxicitidina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Cisplatino/efectos adversos , Doxorrubicina/efectos adversos , Metotrexato/efectos adversos , Vinblastina/efectos adversos , Respuesta Patológica CompletaRESUMEN
PURPOSE: Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. MATERIALS AND METHODS: In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. RESULTS: Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0-1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1-2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. CONCLUSIONS: Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status.
Asunto(s)
Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Anciano , Femenino , Cisplatino , Estudios Retrospectivos , Desoxicitidina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Doxorrubicina , Metotrexato , Vinblastina/efectos adversos , Músculos/patologíaRESUMEN
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.
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Enfermedad de Hodgkin , Adulto , Humanos , Adolescente , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Pronóstico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carga Tumoral , Estudios Retrospectivos , Doxorrubicina/uso terapéutico , Bleomicina/uso terapéutico , Bleomicina/efectos adversos , Dacarbazina/efectos adversos , Vinblastina/uso terapéutico , Vinblastina/efectos adversosRESUMEN
BACKGROUND: The optimal perioperative chemotherapy for patients with muscle-invasive bladder cancer is not defined. The VESPER (French Genito-Urinary Tumor Group and French Association of Urology V05) trial reported improved 3-year progression-free survival with dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) versus gemcitabine and cisplatin (GC) in patients who received neoadjuvant therapy, but not in the overall perioperative setting. In this Article, we report on the secondary endpoints of overall survival and time to death due to bladder cancer at 5-year follow-up. METHODS: VESPER was an open-label, randomised, phase 3 trial done at 28 university hospitals or comprehensive cancer centres in France, in which adults (age ≤18 years and ≤80 years) with primary bladder cancer and histologically confirmed muscle-invasive urothelial carcinoma were randomly allocated (1:1; block size four) to treatment with dd-MVAC (every 2 weeks for a total of six cycles) or GC (every 3 weeks for a total of four cycles). Overall survival and time to death due to bladder cancer (presented as 5-year cumulative incidence of death due to bladder cancer) was analysed by intention to treat (ITT) in all randomly assigned patients. Overall survival was assessed by the Kaplan-Meier method with the treatment groups compared with log-rank test stratified for mode of administration of chemotherapy (neoadjuvant or adjuvant) and lymph node involvement. Time to death due to bladder cancer was analysed with an Aalen model for competing risks and a Fine and Gray regression model stratified for the same two covariates. Results were presented for the total perioperative population and for the neoadjuvant and adjuvant subgroups. The trial is registered with ClinicalTrials.gov, NCT01812369, and is complete. FINDINGS: From Feb 25, 2013, to March 1, 2018, 500 patients were randomly assigned, of whom 493 were included in the final ITT population (245 [50%] in the GC group and 248 [50%] in the dd-MVAC group; 408 [83%] male and 85 [17%] female). 437 (89%) patients received neoadjuvant chemotherapy. Median follow-up was 5·3 years (IQR 5·1-5·4); 190 deaths at the 5-year cutoff were reported. In the perioperative setting (total ITT population), we found no evidence of association of overall survival at 5 years with dd-MVAC treatment versus GC treatment (64% [95% CI 58-70] vs 56% [50-63], stratified hazard ratio [HRstrat] 0·79 [95% CI 0·59-1·05]). Time to death due to bladder cancer was increased in the dd-MVAC group compared with in the GC group (5-year cumulative incidence of death: 27% [95% CI 21-32] vs 40% [34-46], HRstrat 0·61 [95% CI 0·45-0·84]). In the neoadjuvant subgroup, overall survival at 5 years was improved in the dd-MVAC group versus the GC group (66% [95% CI 60-73] vs 57% [50-64], HR 0·71 [95% CI 0·52-0·97]), as was time to death due to bladder cancer (5-year cumulative incidence: 24% [18-30] vs 38% [32-45], HR 0·55 [0·39-0·78]). In the adjuvant subgroup, the results were not conclusive due to the small sample size. Bladder cancer progression was the cause of death for 157 (83%) of the 190 deaths; other causes of death included cardiovascular events (eight [4%] deaths), deaths related to chemotherapy toxicity (four [2%]), and secondary cancers (four [2%]). INTERPRETATION: Our results on overall survival at 5 years were in accordance with the primary endpoint analysis (3-year progression-free survival). We found no evidence of improved overall survival with dd-MVAC over GC in the perioperative setting, but the data support the use of six cycles of dd-MVAC over four cycles of GC in the neoadjuvant setting. These results should impact practice and future trials of immunotherapy in bladder cancer. FUNDING: French National Cancer Institute.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Adulto , Humanos , Masculino , Femenino , Adolescente , Neoplasias de la Vejiga Urinaria/patología , Cisplatino , Vinblastina/efectos adversos , Metotrexato/efectos adversos , Carcinoma de Células Transicionales/tratamiento farmacológico , Gemcitabina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina , Desoxicitidina , Terapia Neoadyuvante/efectos adversos , Músculos/patologíaRESUMEN
The JSH Practical Guidelines for Hematological Malignancies, 2018 expanded edition, newly adopted brentuximab vedotin, doxorubicin, vinblastine, dacarbazine(A+AVD)protocol as a standard treatment for advanced-stage classical Hodgkin lymphoma(CHL). Therefore, this retrospective analysis compared 15 patients who received A+AVD therapy with 21 patients who received doxorubicin, bleomycin, vinblastine, dacarbazine(ABVD)therapy. All patients were newly diagnosed with CHL and received induction therapy between April 2015 and June 2022 in our hospital. All except 1 patient of the A+AVD group had advanced-stage CHL. The median age was 63(23-85)years. The estimated 2-year overall survival of the A+AVD group was better than that of the ABVD group which included 6 patients with clinical stage â ¢ or higher CHL (100% vs 66.7%, p=0.047). In contrast, there was no significant difference in the complete response rate(53.8% vs 100%, p=0.109)between the 2 groups. The overall response rate after first-line treatment(69.2% vs 100%, p=0.255), and the estimated 2-year progression-free survival(70.1% vs 66.7%, p=0.321)between the A+AVD and the ABVD groups were similar.
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Enfermedad de Hodgkin , Humanos , Persona de Mediana Edad , Enfermedad de Hodgkin/tratamiento farmacológico , Brentuximab Vedotina/efectos adversos , Vinblastina/uso terapéutico , Vinblastina/efectos adversos , Dacarbazina/uso terapéutico , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Bleomicina/uso terapéutico , Estadificación de NeoplasiasRESUMEN
PURPOSE: This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL). METHODS: The PubMed, Scopus, Web of Science core collection, and Embase databases were searched until July 3, 2022. We included published full economic evaluation studies on BV for treating patients with HL. The methodological quality of the studies was assessed using the Quality of Health Economic Studies (QHES) checklist. Meanwhile, we used qualitative synthesis to analyze the findings. We converted the incremental cost-effectiveness ratios (ICERs) to the value of the US dollar in 2022. RESULTS: Eight economic evaluations met the study's inclusion criteria. The results of three studies that compared BV plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) front-line therapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) showed that BV is unlikely to be cost-effective as a front-line treatment in patients advanced stage (III or IV) HL. Four studies investigated the cost-effectiveness of BV in patients with relapsed or refractory (R/R) HL after autologous stem cell transplantation (ASCT). BV was not cost-effective in the reviewed studies at accepted thresholds. In addition, the adjusted ICERs ranged from $65,382 to $374,896 per quality-adjusted life-year (QALY). The key drivers of cost-effectiveness were medication costs, hazard ratio for BV, and utilities. CONCLUSION: Available economic evaluations show that using BV as front-line treatment or consolidation therapy is not cost-effective based on specific ICER thresholds for patients with HL or R/R HL. To decide on this orphan drug, we should consider other factors such as existence of alternative treatment options, clinical benefits, and disease burden.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/etiología , Brentuximab Vedotina/uso terapéutico , Análisis Costo-Beneficio , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/uso terapéutico , Vinblastina/uso terapéutico , Vinblastina/efectos adversos , Dacarbazina/uso terapéutico , Dacarbazina/efectos adversos , Trasplante AutólogoRESUMEN
La enfermedad de Erdheim-Chester (EEC) es una patología poco frecuente, caracterizada por presentar infiltración xantogranulomatosa sistémica, con afección de diversos sistemas incluido el óseo. La EEC se encuentra descripta dentro de las enfermedades osteocon-densantes (EO), las cuales se reconocen por presentar aumento de la masa ósea y compromiso tanto de huesos largos como planos. La presentación clínica de la EEC es variada: puede presentar desde un curso indolente hasta manifestaciones multisistémicas. Las características radiológicas son de gran importancia para establecer su diagnóstico. Presentamos una paciente con EEC, con esclerosis bilateral de huesos largos, que exhibe algunas características diferenciales con relación a otros casos reportados: a) afectación exclusivamente ósea a 10 años de evolución, b) compromiso bilateral y simétrico de distinta magnitud, c) esclerosis cortical endóstica y perióstica, d) signos radiológicos sugestivos de periostitis, d) ausencia de compromiso metafisario, e) ausencia de actividad metabólica de las lesiones en las imágenes de 18F-FDG PET/CT.Conclusión: la presencia de lesiones osteocondensantes bilaterales exclusivamente en huesos largos deben hacer sospechar EEC. La ausencia de compromiso metafisario y de actividad metabólica en 18F-FDG PET/CT ha sido raramente descripta. (AU)
Erdheim - Chester disease (ECD) is a rare disease, characterized by systemic xanthogranulomatous infiltration, with involvement of various organs including bone. ECD is described within the sclerosing bone disorders, which are recognized for presenting increased bone mass and involvement of both long and flat bones. The clinical presentation of ECD is diverse, ranging from an asymptomatic course to multisystemic manifestations. Radiological features are of great importance to establish the diagnosis. We describe here a patient with ECD, with bilateral sclerosis of long bones that presents some differential characteristics in relation to other reported cases: a) exclusively bone involvement at 10 years of evolution, b) bilateral and symmetric involvement of different magnitude, c) endosteal and periosteal cortical sclerosis d) radiological signs suggestive of periostitis, d) absence of metaphyseal involvement, e) absence of metabolic activity of the lesions in 18F-FDG PET/CT.Conclusion: the presence of bilateral osteosclerosis exclusively in long bones should lead to suspect ECD. The absence of metaphyseal involvement and metabolic activity in 18F-FDG PET/CT have been rarely described. (AU)
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Humanos , Femenino , Persona de Mediana Edad , Esclerosis/etiología , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Fémur/patología , Húmero/patología , Vinblastina/efectos adversos , Biopsia con Aguja , Prednisona/uso terapéutico , Radiografía , Cintigrafía , Interferones/efectos adversos , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Tomografía de Emisión de Positrones , Manejo del Dolor , Ácido Zoledrónico/administración & dosificaciónRESUMEN
PURPOSE: While previous retrospective or phase II studies in Western populations showed that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) as neoadjuvant chemotherapy (NAC) was beneficial, no studies have been reported in Asian populations. This prospective phase II study aimed to evaluate efficacy and safety of ddMVAC in Korean patients with muscle-invasive bladder cancer (MIBC) or locally advanced urothelial cancer (UC). MATERIALS AND METHODS: Patients with MIBC (cT2-4aN0M0) or locally advanced UC (cTanyN1-3M0) eligible for radical cystectomy (RC) were enrolled prospectively. The participants were treated with four cycles of ddMVAC with pegfilgrastim every 2 weeks. The primary endpoint was pathologic response rate (≤ypT1N0). Secondary endpoints were pathologic complete response (pCR, ypT0N0), relapse-free survival (RFS), overall survival (OS), and safety. RESULTS: Among 24 patients enrolled between December 2019 and August 2021, 23 were evaluable (52%, cT2-4aN0; 48%, cTanyN1-3). Eighteen patients (78%) completed four cycles of ddMVAC, while remaining five patients experienced early discontinuation. Dose modification (91%) and dose delay (70%) occurred, and the dose intensity of ddMVAC was 79%. Nineteen patients underwent RC and four patients declined. Of 19 patients who underwent RC, eight patients (42%) achieved ≤ypT1N0. With a median follow-up of 22.8 months, the median RFS was 13.5 months (95% CI, not yet evaluable) and the median OS was 28.9 months (95% confidence interval, 19.9-37.9). CONCLUSION: Our study showed substantial efficacy and safety of ddMVAC, even in patients with locally advanced UC. The ddMVAC still should be a promising option as NAC in Asian patients with UC.
Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Vejiga Urinaria/patología , Cistectomía , Terapia Neoadyuvante/efectos adversos , Estudios Retrospectivos , Estudios Prospectivos , Resultado del Tratamiento , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Cisplatino/efectos adversos , Músculos/patología , República de Corea , Invasividad Neoplásica/patología , Vinblastina/efectos adversosRESUMEN
BACKGROUND: Despite the advancements in multiagent chemotherapy in the past years, up to 10% of Hodgkin's Lymphoma (HL) cases are refractory to treatment and, after remission, patients experience an elevated risk of death from all causes. These complications are dependent on the treatment and therefore an increase in the prognostic accuracy of HL can help improve these outcomes and control treatment-related toxicity. Due to the low incidence of this cancer, there is a lack of works comprehensively assessing the predictability of treatment response, especially by resorting to machine learning (ML) advances and high-throughput technologies. METHODS: We present a methodology for predicting treatment response after two courses of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy, through the analysis of gene expression profiles using state-of-the-art ML algorithms. We work with expression levels of tumor samples of Classical Hodgkin's Lymphoma patients, obtained through the NanoString's nCounter platform. The presented approach combines dimensionality reduction procedures and hyperparameter optimization of various elected classifiers to retrieve reference predictability levels of refractory response to ABVD treatment using the regulatory profile of diagnostic tumor samples. In addition, we propose a data transformation procedure to map the original data space into a more discriminative one using biclustering, where features correspond to discriminative putative regulatory modules. RESULTS: Through an ensemble of feature selection procedures, we identify a set of 14 genes highly representative of the result of an fuorodeoxyglucose Positron Emission Tomography (FDG-PET) after two courses of ABVD chemotherapy. The proposed methodology further presents an increased performance against reference levels, with the proposed space transformation yielding improvements in the majority of the tested predictive models (e.g. Decision Trees show an improvement of 20pp in both precision and recall). CONCLUSIONS: Taken together, the results reveal improvements for predicting treatment response in HL disease by resorting to sophisticated statistical and ML principles. This work further consolidates the current hypothesis on the structural difficulty of this prognostic task, showing that there is still a considerable gap to be bridged for these technologies to reach the necessary maturity for clinical practice.