RESUMEN
Sézary syndrome is an aggressive and disseminated form of cutaneous T-cell lymphoma associated with dismal prognosis in which the histone deacetylase inhibitor romidepsin has shown remarkable activity as a single agent. However, clinical responses to romidepsin are typically transient, highlighting the need for more effective therapies. In this study, we show synergistic antilymphoma effects of romidepsin in combination with mechlorethamine, an alkylating agent, in cutaneous T-cell lymphoma cell lines and primary samples with strong antitumor effects in an in vivo model of Sézary syndrome. Mechanistically, gene expression profiling points to abrogation of Jak/signal transducer and activator of transcription (STAT) signaling as an important mediator of this interaction. Consistently, the combination of mechlorethamine plus romidepsin resulted in downregulation of STAT5 phosphorylation in romidepsin-sensitive cell lines and primary Sézary syndrome samples, but not in romidepsin-resistant tumors. Moreover, in further support of Jak/STAT signaling as a modulator of romidepsin activity in cutaneous T-cell lymphoma, treatment with romidepsin in combination with Jak inhibitors resulted in markedly increased therapeutic responses. Overall, these results support a role for romidepsin plus mechlorethamine in combination in the treatment of cutaneous T-cell lymphoma and uncover a previously unrecognized role for Jak/STAT signaling in the response to romidepsin and romidepsin-based combination therapies in Sézary syndrome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Depsipéptidos/administración & dosificación , Inhibidores de las Cinasas Janus/farmacología , Linfoma Cutáneo de Células T/tratamiento farmacológico , Mecloretamina/administración & dosificación , Factores de Transcripción STAT/antagonistas & inhibidores , Neoplasias Cutáneas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Sinergismo Farmacológico , Humanos , Ratones , Factores de Transcripción STAT/fisiología , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking. OBJECTIVE: Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. METHODS: This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA-IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. RESULTS: In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. CONCLUSIONS: This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mecloretamina/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Administración Oral , Anciano , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Geles , Humanos , Masculino , Mecloretamina/efectos adversos , Persona de Mediana Edad , Micosis Fungoide/diagnóstico , Micosis Fungoide/psicología , Estadificación de Neoplasias , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/psicología , Resultado del Tratamiento , Estados UnidosAsunto(s)
Mecloretamina/farmacocinética , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Absorción Fisiológica , Administración Cutánea , Adulto , Anciano , Femenino , Geles , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Micosis Fungoide/patología , Pomadas , Piel/metabolismo , Piel/patología , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: The pivotal 201 Study investigated chlormethine/mechlorethamine gel treatment for patients with early stage disease mycosis fungoides and demonstrated the treatment was not inferior to chlormethine ointment. However, overall response rates do not provide information about response patterns. The study objective was to assess the value of by-time analysis of clinical response data in visualizing response over time. METHODS: This post hoc analysis re-evaluated chlormethine efficacy using a by-time approach that investigated the trend to treatment response and permitted assessment of response, both monthly between 1 and 6 months, and once every 2 months between 7 and 12 months, over the course of 1 year. In addition, very good partial response was redefined as a ≥ 75% response. RESULTS: By-time analyses of Composite Assessment of Index Lesion Severity (CAILS) and modified severity-weighted assessment tool (mSWAT) showed response rates at 1 month (respectively, 8.5% and 5.9%) that increased over time to peak at 10 months (78.9% and 54.4%). Early, intermittent, and late response patterns were observed. In total, 32.5% of patients experienced very good partial response over 2 consecutive visits, indicating that â¼ 33% of patients could expect to have very good to complete response within 1 year. CONCLUSION: By-time analysis for clinical response provides complementary information to traditional overall response rate data regarding response peak time and changes over time.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Mecloretamina/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos Alquilantes/efectos adversos , Ensayos Clínicos Fase II como Asunto , Geles , Humanos , Mecloretamina/efectos adversos , Micosis Fungoide/diagnóstico , Estadificación de Neoplasias , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Cutáneas/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Langerhans cell histiocytosis (LCH) limited to the skin is rare in adult patients. Given the challenges of prospective clinical trials for this rare disease, there is paucity in data to guide the management of cutaneous LCH. Topical nitrogen mustard is a possible treatment for cutaneous LCH with positive responses in five known adult cases in the literature. In this report, we present two adult patients with recalcitrant cutaneous LCH and no evidence of systemic involvement who had rapid and complete response on topical nitrogen mustard therapy. We provide support for topical nitrogen mustard as a treatment option for primary cutaneous LCH which may spare patients from requiring systemic immunosuppressive treatments. J Drugs Dermatol. 2020;19(8):803-805. doi:10.36849/JDD.2020.4943.
Asunto(s)
Alquilantes/administración & dosificación , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Mecloretamina/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/patología , Humanos , Piel/efectos de los fármacos , Piel/patología , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/patología , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to extensively describe the epidemiological, clinical and therapeutic outcomes of adolescents and young adults (AYA) population with classical Hodgkin Lymphoma (cHL). Then, a comparison between AYAs and adults and between the subgroups of AYAs treated with the same adult protocol was accomplished to further inform on optimal therapy approach of choice for adolescent patients. MATERIAL AND METHODS: In this mono-centric, retrospective study, we reviewed the medical records. We analyzed 112 consecutive North Tunisian patients, including 66 AYAs (15 to 39 years) and 46 adults (≥40years) affected by cHL treated from 2000 to 2015 at Salah Azaiez Institute. Then, we performed a comparative analysis between AYA and 46 adult patients and a subgroup analysis between adolescents and young adults. All patients were treated according to the national protocol for HL, edited by the Tunisian Society of Hematology. The treatment included chemotherapy and involved-field radiotherapy (RT) at a dose of 20 or 30 Grays (Gy) for responders and 36Gy for non-responders. RESULTS: AYA patients presented with adverse features with nodular sclerosis subtype (p=3.88×10-02) and mediastinal mass involvement (p=9.40×10-04). At a median follow-up of 51 and 32 months for AYAs and adults, respectively, no statistical difference in terms of 3 and 5-years overall survival (OS) and event-free survival (EFS) was shown. Using the Kaplan-Meier method, in AYAs, the ABVD regimen has an impact on 3-years EFS (p=4.63×10-02). The 36Gy RT was associated with the best 3-years EFS (p=9.24×10-03). Besides, AYA patients with advanced-stage had the worst 3-years OS (76%) (p=2.41×10-02). Although the adolescents and young adults shared similar clinical presentation, we noted that the adolescent group had the worst 3-years EFS (48%), but the best 3-years OS (91%). We identified 15% of primary refractory patients and a rate of toxicity of 5.3% in AYA. CONCLUSION: The treatment approach used is well tolerated by adult patients. However, the AYA patients and particularly adolescent subgroup had more advanced disease at diagnosis and should be treated more intensively in dedicated units. RT dose<36Gy and ABVD chemotherapy were associated with lower EFS in this population.
Asunto(s)
Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Mecloretamina/administración & dosificación , Neoplasias del Mediastino/patología , Persona de Mediana Edad , Órganos en Riesgo/efectos de la radiación , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Dosificación Radioterapéutica , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Túnez/epidemiología , Vinblastina/administración & dosificación , Vincristina/administración & dosificación , Adulto JovenAsunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Erupciones por Medicamentos/epidemiología , Mecloretamina/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/efectos adversos , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Femenino , Geles , Humanos , Masculino , Mecloretamina/efectos adversos , Persona de Mediana Edad , Micosis Fungoide/complicaciones , Micosis Fungoide/diagnóstico , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
Lymphomatoid papulosis (LyP) is a paraneoplastic primary cutaneous CD30+ lymphoproliferative disorder (LPD) that has been associated with malignant lymphomas, most commonly mycosis fungoides (MF). We observed 10 patients with MF who developed severe inflammation after using nitrogen-mustard (NM) gel from 1 to 8 months and who developed LyP. We hypothesized that NM gel produced local inflammation, which induced CD30 expression in malignant T cells in situ leading to the appearance of LyP papules. The high frequency of induction of LyP lesions in patients with severe inflammation while on treatment with NM gel suggests an association between inflammatory stimuli and development of LyP. Our observation provides insight into the pathogenesis of CD30+ LPD.
Asunto(s)
Antineoplásicos Alquilantes/efectos adversos , Papulosis Linfomatoide/inmunología , Mecloretamina/efectos adversos , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Femenino , Geles , Humanos , Antígeno Ki-1/inmunología , Antígeno Ki-1/metabolismo , Papulosis Linfomatoide/inducido químicamente , Papulosis Linfomatoide/patología , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Adulto JovenRESUMEN
Nitrogen mustard (NM) is among the earliest drugs used to treat malignant tumors and it kills tumor cells by cross-linking DNA. Unfortunately, because of the short half-life and unfavorable selectivity, NM causes significant damage to normal tissues. As NM can increase the levels of reactive oxygen species (ROS) in tumor cells, a ROS-activated nitrogen mustard prodrug (NM-Pro) was synthesized and mixed with NM at a specific ratio to obtain an "NM-ROS-NM-Pro-NM" positive feedback system, which ultimately achieves a specific lethal effect on hematological neoplasms. The further encapsulation of NM/NM-Pro in liposomes allows the sustained release of the drug and prolongs the residence time in vivo. Here, we prepared stable liposomes with a uniform particle size of 170.6 ± 2.2 nm. The optimal ratio of NM to NM-Pro in this study was 2:1. The active drug NM in the NM/NM-Pro system continuously stimulated ROS production by the cells, which in turn further activated the NM-Pro to continuously generate NM. The positive feedback pathway between the NM and NM-Pro resulted in the specific death of tumor cells. Furthermore, the K562 hematological neoplasm model was utilized to evaluate the therapeutic effect of NM/NM-Pro liposomes in vivo. After encapsulation in liposomes, the targeting of tumor cells was increased approximately two times compared with that of normal cells, and NM/NM-Pro liposomes exhibited reduced toxicity, without an increase in drug activity compared to the NM/NM-Pro combination. The NM/NM-Pro delivery system exerts a positive feedback effect on ROS production in tumor cells and displays good potential for the specific killing of hematoma cells.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Retroalimentación Fisiológica , Neoplasias Hematológicas/tratamiento farmacológico , Mecloretamina/administración & dosificación , Profármacos/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Animales , Antineoplásicos Alquilantes/farmacocinética , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Liberación de Fármacos , Femenino , Humanos , Células K562 , Liposomas , Mecloretamina/farmacocinética , Ratones , Tamaño de la Partícula , Profármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
BACKGROUND: Topical chlormethine has been widely used in the early stages of mycosis fungoides for many years. Cutaneous reactions (skin irritation and itch) are the most frequent adverse effects. Herein we report a rare side effect: severe necrotic leg ulcers. PATIENTS AND METHODS: An 82-year-old woman with a history of high blood pressure developed hyperalgesic necrotic ulcers on the lower limbs following local trauma one month after initiation of topical chlormethine (Valchlor®) to treat mycosis fungoides. Aetiological examination showed moderate peripheral arterial disease which, while constituting an aggravating factor, did not account fully for these skin ulcers. Moreover, drug-induced ulcer was suspected on account of the chronology. Dermal corticoids and topical treatment were prescribed in place of chlormethine and led to a favourable outcome. CONCLUSION: Incrimination of chlormethine was based on the chronological and semiological criteria. This is the first published case of leg ulceration induced by Valchlor®.
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Antineoplásicos Alquilantes/efectos adversos , Úlcera de la Pierna/inducido químicamente , Úlcera de la Pierna/patología , Mecloretamina/efectos adversos , Piel/patología , Administración Tópica , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Femenino , Humanos , Mecloretamina/administración & dosificación , Necrosis/inducido químicamenteAsunto(s)
Fármacos Dermatológicos/administración & dosificación , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Mecloretamina/administración & dosificación , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Adolescente , Dermatosis de la Mano/tratamiento farmacológico , Humanos , MasculinoRESUMEN
Nitrogen mustard is a chemotherapeutic agent that has a well-documented safety and efficacy profile in the treatment of cutaneous T-cell lymphoma. Development of nitrogen mustard formulations and treatment regimens has been studied extensively over the last 40 years. In the last 5 years, a new gel formulation has been developed that is associated with a decrease in delayed hypersensitivity reactions. The authors in this review found that while the gel formulation may result in a decrease of allergic contact dermatitis, this advantage has been replaced by a higher number of irritant contact reactions and a decrease in complete response rate. The gel formulation has a complete response rate of 13.8%, which is a decrease in efficacy when compared to aqueous-based preparations of similar concentrations.
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Antineoplásicos Alquilantes/administración & dosificación , Mecloretamina/administración & dosificación , Micosis Fungoide/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Cutánea , Antineoplásicos Alquilantes/efectos adversos , Erupciones por Medicamentos/etiología , Geles , Humanos , Mecloretamina/efectos adversos , Micosis Fungoide/inmunología , Micosis Fungoide/patología , Factores de Riesgo , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
Objectives The goals of this retrospective study were to evaluate the use of mechlorethamine, vincristine, melphalan and prednisolone (MOMP) chemotherapy for rescue of feline lymphoma, to describe the protocol's toxicity and to determine prognostic indicators for progression-free survival. Methods The medical records of 12 cats treated with MOMP chemotherapy at the University of Tennessee Veterinary Medical Center between 2007 and 2017 were evaluated. Parameters assessed included lymphoma cell size, anatomical location, number of previous chemotherapy drugs and number of previous rescue protocols received. Chemotherapy-related toxicity was also described. Results Seven of 12 cats responded to this rescue protocol. Three cats experienced complete response and four cats achieved partial response for a median duration of 39 days (range 14-345 days). Cats that achieved complete response had a significantly longer median progression-free survival than cats that did not respond to treatment. Five of 12 cats developed hematologic toxicity (neutropenia) and one cat developed gastrointestinal toxicity. Toxicity was mild in most cases; no cats needed to be hospitalized. Neutropenia was associated with increased progression-free survival. Conclusions and relevance MOMP is a safe and effective rescue chemotherapy protocol for cats with relapsing and refractory lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Linfoma/veterinaria , Recurrencia Local de Neoplasia/veterinaria , Animales , Enfermedades de los Gatos/mortalidad , Gatos , Supervivencia sin Enfermedad , Femenino , Linfoma/tratamiento farmacológico , Masculino , Mecloretamina/administración & dosificación , Melfalán/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Prednisolona/administración & dosificación , Registros/veterinaria , Estudios Retrospectivos , Tennessee , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: To determine whether the risk of secondary breast cancer (SBC) is reduced in women with Hodgkin lymphoma (HL) treated with smaller field radiation therapy (SFRT) versus mantle field radiation therapy (MRT). METHODS AND MATERIALS: We used the BC Cancer Agency (BCCA) Lymphoid Cancer Database to identify female patients treated for HL between January 1961 and December 2009. Radiation therapy volumes were categorized as MRT or SFRT, which included involved field, involved site, or involved nodal radiation therapy. SBC risk estimates were compared using competing risk analysis and Fine and Gray multivariable model: MRT ± chemotherapy, SFRT ± chemotherapy, or chemotherapy-only. RESULTS: Of 734 eligible patients, 75% of the living patients have been followed up for more than 10 years, SBC has developed in 54, and 15 have died of breast cancer. The 20-year estimated risks (competing risk cumulative incidence) for SBC differed significantly: MRT 7.5% (95% confidence interval [CI] 4.4%-11.5%), SFRT 3.1% (95% CI 1.0%-7.7%), and chemotherapy-only 2.2% (95% CI 1.0%-4.8%) (P=.01). Using a Fine and Gray model to control for death and patients lost to follow-up, MRT was associated with a higher risk of SBC (hazard ratio [HR] = 2.9; 95% CI 1.4%-6.0%; P=.004) compared with chemotherapy-only and with SFRT (HR = 3.3; 95% CI 1.3%-8.4%; P=.01). SFRT was not associated with a greater risk of SBC compared with chemotherapy-only (HR = 0.87; 95% CI 0.28%-2.66%; P=.80). CONCLUSION: This study confirms that large-volume MRT is associated with a markedly increased risk of SBC; however, more modern small-volume RT is not associated with a greater risk of SBC than chemotherapy alone.
Asunto(s)
Neoplasias de la Mama/etiología , Enfermedad de Hodgkin/radioterapia , Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Adolescente , Adulto , Análisis de Varianza , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Colombia Británica/epidemiología , Causas de Muerte , Niño , Intervalos de Confianza , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Incidencia , Perdida de Seguimiento , Irradiación Linfática/efectos adversos , Mecloretamina/administración & dosificación , Mecloretamina/efectos adversos , Menopausia Prematura , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patología , Enfermedades del Ovario/etiología , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Radioterapia/efectos adversos , Radioterapia/métodos , Medición de Riesgo , Sobrevivientes , Factores de Tiempo , Vincristina/administración & dosificación , Vincristina/efectos adversos , Adulto JovenAsunto(s)
Micosis Fungoide/patología , Neoplasias Cutáneas/patología , Administración Cutánea , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Biomarcadores de Tumor/análisis , Biopsia , Humanos , Inmunohistoquímica , Masculino , Mecloretamina/administración & dosificación , Micosis Fungoide/química , Micosis Fungoide/tratamiento farmacológico , Estadificación de Neoplasias , Inducción de Remisión , Neoplasias Cutáneas/química , Neoplasias Cutáneas/tratamiento farmacológico , Factores de Tiempo , Resultado del TratamientoRESUMEN
In 1959, McFarland and colleagues reported one of the earliest trials pioneering the use of high-dose chemotherapy and autologous bone marrow transplantation in patients with malignant disease. With the goal of circumventing marrow toxicity, marrow was collected and stored at room temperature for 24 hours while patients underwent cytotoxic therapy. Following the administration of "super" doses of nitrogen mustard, autologous bone marrow was infused into 2 patients with "lymphosarcomatosis" and 3 with Hodgkin disease. Although 2 patients died from infection, 3 recovered and experienced brief remissions. These results were considered to be highly encouraging and helped to propel further studies leading to the growth of the field.
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Antineoplásicos/administración & dosificación , Trasplante de Médula Ósea/métodos , Enfermedad de Hodgkin/terapia , Oncología Médica/historia , Terapia Combinada , Historia del Siglo XX , Humanos , Mecloretamina/administración & dosificación , Inducción de Remisión , Trasplante Autólogo/métodos , Resultado del TratamientoRESUMEN
This article highlights the important collaboration between the U.S. NCI in Bethesda, Maryland and the Istituto Tumori in Milan, Italy that had a major impact on the development of curative regimens for breast cancer, Hodgkin's disease and diffuse large B cell lymphoma.In addition to his contribution to developing new therapies, Gianni Bonadonna played an important role in bringing highly focused, disciplined, ethical clinical trials to the European continent.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Enfermedad de Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Oncología Médica/historia , Amsacrina/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/historia , Bleomicina/administración & dosificación , Neoplasias de la Mama/historia , Neoplasias de la Mama/mortalidad , Ensayos Clínicos como Asunto/historia , Conducta Cooperativa , Ciclofosfamida/administración & dosificación , Ciclofosfamida/historia , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/historia , Historia del Siglo XX , Historia del Siglo XXI , Enfermedad de Hodgkin/historia , Enfermedad de Hodgkin/mortalidad , Humanos , Italia , Tablas de Vida , Linfoma no Hodgkin/historia , Linfoma no Hodgkin/mortalidad , Masculino , Mecloretamina/administración & dosificación , Mecloretamina/historia , Metotrexato/administración & dosificación , Metotrexato/historia , National Cancer Institute (U.S.) , Prednisona/administración & dosificación , Prednisona/historia , Procarbazina/administración & dosificación , Procarbazina/historia , Estados Unidos , Vincristina/administración & dosificación , Vincristina/historiaRESUMEN
Hodgkin lymphoma is a rare lymphoid malignancy affecting â¼9,200 new patients in the United States annually. Progress in the management of this disease over the past 50 years has been remarkable and the prognosis of this malignancy has changed from a uniformly fatal process to one in which the vast majority of patients are expected to be cured. This remarkable progress has been due to the use of combination approaches incorporating chemotherapy and radiation therapy, and now more recently antibody-drug conjugates and immune checkpoint inhibitors. The goal for the future is to develop treatment combinations that successfully treat all patients and markedly decrease the long-term side effects.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Ensayos Clínicos como Asunto , Dacarbazina/administración & dosificación , Dacarbazina/efectos adversos , Dacarbazina/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Mecloretamina/administración & dosificación , Mecloretamina/efectos adversos , Mecloretamina/uso terapéutico , Terapia Molecular Dirigida , Prednisona/administración & dosificación , Prednisona/efectos adversos , Prednisona/uso terapéutico , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Procarbazina/uso terapéutico , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Vincristina/administración & dosificación , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (MF-CTCL). Quality nursing care is necessary for effective diagnosis and treatment of patients with MF-CTCL. Early-stage MF-CTCL (stages Ia and Ib) is most often managed in both dermatology and multidisciplinary settings. These stages can be effectively controlled by skin-directed therapies such as mechlorethamine gel (Valchlor®). Topical mechlorethamine has been used since the 1940s as an alkylating agent; however, compounded formulas have disadvantages that limit patient compliance. In contrast, newly approved mechlorethamine gel has demonstrated an efficacious and well-tolerated profile that has longer stability and is quicker to dry than its compounded counterpart. OBJECTIVES: This article aims to provide recommendations for optimal nursing care of patients who have been diagnosed with stage Ia or Ib MF-CTCL. METHODS: Four real-world patient cases are examined, along with practical considerations for the use of mechlorethamine gel to treat patients with MF-CTCL. FINDINGS: Nurses can promote patient adherence through specific interventions and strategies, such as education about mechlorethamine gel, its mechanism of action, and safety and efficacy, as well as connecting patients with patient assistance programs or other supportive services.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Mecloretamina/uso terapéutico , Micosis Fungoide/tratamiento farmacológico , Cooperación del Paciente , Administración Tópica , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/administración & dosificación , Geles , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Micosis Fungoide/enfermeríaRESUMEN
The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP (P = 0·0001) and OS (P < 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.