RESUMEN
This review highlights the story of how methotrexate (MTX), a drug discovered for the treatment of childhood leukemia, became the mainstay of treatment and the standard-of-care for rheumatoid arthritis (RA) and was also found useful for several additional related rheumatological diseases. As against several synthetic disease-modifying antirheumatic drugs (csDMARDs) for treating RA that were discovered serendipitously, the use of low-dose MTX (LD-MTX) was based on sound reasoning and astute observations made in the 1940s and 1950s. The difference between high-dose MTX (HD-MTX) used in the treatment of childhood leukaemia and other malignancies as against LD-MTX used in rheumatology is emphasized.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Descubrimiento de Drogas , Metotrexato/uso terapéutico , Reumatología , Animales , Antimetabolitos Antineoplásicos/uso terapéutico , Antirreumáticos/efectos adversos , Antirreumáticos/historia , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/historia , Descubrimiento de Drogas/historia , Historia del Siglo XX , Humanos , Metotrexato/efectos adversos , Metotrexato/historia , Reumatología/historia , Resultado del TratamientoAsunto(s)
Antiinflamatorios/historia , Antineoplásicos/historia , Leucemia/historia , Mercaptopurina/historia , Metotrexato/historia , Prednisona/historia , Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Niño , Historia del Siglo XX , Humanos , Leucemia/tratamiento farmacológico , Mercaptopurina/uso terapéutico , Metotrexato/uso terapéutico , Prednisona/uso terapéutico , Inducción de RemisiónRESUMEN
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.
Asunto(s)
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
No disponible
Asunto(s)
Humanos , Masculino , Femenino , Artritis Reumatoide/epidemiología , Artritis Reumatoide/prevención & control , Reumatología/historia , Reumatología/métodos , Reumatología/tendencias , Metotrexato/historia , Metotrexato/uso terapéutico , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/historiaRESUMEN
Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/historia , Oncología Médica/historia , Pediatría/historia , Leucemia-Linfoma Linfoblástico de Células Precursoras/historia , Ensayos Clínicos Controlados Aleatorios como Asunto/historia , Asparaginasa/historia , Niño , Ciclofosfamida/historia , Citarabina/historia , Daunorrubicina/historia , Europa (Continente) , Alemania , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Mercaptopurina/historia , Metotrexato/historia , Prednisona/historia , Vincristina/historiaRESUMEN
A little more than half a century ago, young women were frequently dying of reproductive sequelae such as ectopic pregnancies and gestational trophoblastic disease. Mortality from these conditions was as high as 90% in the case of metastatic choriocarcinoma. If lives could be saved, it was in the operating theater and often at the expense of future reproductive potential. By the 1940s, however, targeted chemotherapy was starting to be explored, and the development of methotrexate for the treatment of childhood leukemia in 1949 eventually resulted in an unexpected, but nevertheless long and happy association with the field of gynecology. Here we trace the origins of methotrexate and how it came to be an effective medical treatment for two life-threatening gynecologic conditions. It illustrates how the contributions of many clinicians and scientists from many disciplines, over the greater part of a century, come together to improve the care of a single patient today.
Asunto(s)
Antimetabolitos Antineoplásicos/historia , Neoplasias de los Genitales Femeninos/historia , Ginecología/historia , Metotrexato/historia , Embarazo Ectópico/historia , Antimetabolitos Antineoplásicos/uso terapéutico , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Historia del Siglo XX , Humanos , Metotrexato/uso terapéutico , Embarazo , Embarazo Ectópico/tratamiento farmacológicoRESUMEN
The history of the rheumatologic use of methotrexate until the 1990s will be reviewed, beginning with its pharmacology, with the focus on rheumatoid arthritis (RA). The insufficient availability of cortisone in the 1950s as well as the early recognition of its potential toxicity stimulated searches for alternative anti-inflammatory drugs. Two related derivatives of folic acid, aminopterin and amethopterin (MTX,) were found to give rapid symptomatic relief in cases of psoriasis vulgaris and psoriatic arthritis. For several years MTX was used primarily to treat psoriasis, and the dermatologic treatment protocols came to be used by rheumatologists. Giving MTX weekly rather than daily was found to diminish the risk of toxic effects. MTX became favoured over cyclophosphamide because of its lack of carcinogenicity, and although azathioprine lacked the hepatotoxicity of MTX, its anti-rheumatic effects were considered to be somewhat weaker. Although trials of MTX for the treatment of severe RA began in the 1960s, the first placebo-controlled study of MTX in RA was reported in 1985 and a comparison with Myochrysine in 1987. MTX has replaced gold compounds because it has been found to be more rapidly effective and better tolerated. The mechanisms of its anti-rheumatic effects remain incompletely explained, as are explanations of instances of its failure. Its recent use in combination with anti-TNFα agents appears to be another therapeutic advance.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Metotrexato/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Antirreumáticos/efectos adversos , Antirreumáticos/historia , Artritis Reumatoide/historia , Artritis Reumatoide/inmunología , Productos Biológicos/efectos adversos , Productos Biológicos/historia , Quimioterapia Combinada , Medicina Basada en la Evidencia , Historia del Siglo XX , Humanos , Metotrexato/efectos adversos , Metotrexato/historia , Resultado del TratamientoRESUMEN
The development of methotrexate (MTX) as a therapy for rheumatoid arthritis (RA) evolved initially from positive case reports, uncontrolled case series and then several decades later placebo controlled studies followed by active comparator studies. These studies established MTX as a major therapy for RA. The importance of MTX in the treatment paradigm has only been enhanced over the past decade by the increased efficacy observed when small molecules and biologics are added to MTX. Since the first randomised studies were performed in the 1980s, MTX has now become the most well-studied disease modifying therapy to date and the most popular drug worldwide in the treatment of RA. This chapter will review the history of the development of MTX in RA.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Ensayos Clínicos como Asunto , Medicina Basada en la Evidencia , Metotrexato/uso terapéutico , Antirreumáticos/historia , Artritis Reumatoide/historia , Ensayos Clínicos como Asunto/historia , Medicina Basada en la Evidencia/historia , Historia del Siglo XX , Humanos , Metotrexato/historia , Resultado del TratamientoRESUMEN
In this chapter, we review the use of DMARDs in several clinical RA cohorts and databases between the 1970s and the 2000s. The DMARD profile in the QUEST-RA database provides an overview of clinical use of MTX in recent years in 25 countries. The data show that (I) MTX is currently the most frequently used DMARD in RA, and (II) that this development has taken about 20 years to emerge.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Antirreumáticos/historia , Artritis Reumatoide/historia , Bases de Datos como Asunto , Utilización de Medicamentos , Revisión de la Utilización de Medicamentos , Medicina Basada en la Evidencia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Metotrexato/historia , Resultado del TratamientoAsunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Metotrexato/administración & dosificación , Terapia Neoadyuvante , Osteosarcoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/historia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/historia , Esquema de Medicación , Historia del Siglo XX , Humanos , Metotrexato/historia , Terapia Neoadyuvante/historia , Terapia Neoadyuvante/métodos , Osteosarcoma/historia , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Fármacos Dermatológicos/uso terapéutico , Metotrexato/uso terapéutico , Psoriasis/tratamiento farmacológico , Fármacos Dermatológicos/historia , Predicción , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Programas Controlados de Atención en Salud , Metotrexato/historia , Pautas de la Práctica en Medicina , Psoriasis/historia , Calidad de VidaRESUMEN
Dr. Roy Hertz is one of two scientists credited with discovering the first medical cure of a solid cancer. This paper presents a biographical history of Dr. Hertz and discusses his roles in the discovery of a cure for choriocarcinoma and as a pioneer for future research in cancer chemotherapy. This biography not only serves as a testament to the pioneering individuals in the field of chemotherapeutics but also represents the unique blend of medical, pharmacological, and physiological histories that led to the profound discovery. The timing and significance of the work of Drs. Hertz and Li cannot be overestimated. Their discovery was a spectacular success, demonstrating proof of the principle that chemotherapy can cure metastatic cancer and that an almost uniformly fatal cancer in young patients could be cured with a single chemotherapeutic agent, which stands as one of the greatest achievements in cancer research.
Asunto(s)
Antimetabolitos Antineoplásicos/historia , Coriocarcinoma/historia , Metotrexato/historia , Antimetabolitos Antineoplásicos/uso terapéutico , Coriocarcinoma/tratamiento farmacológico , Coriocarcinoma/secundario , Historia del Siglo XX , Humanos , Oncología Médica/historia , Metotrexato/uso terapéutico , National Institutes of Health (U.S.)/historia , Estados UnidosAsunto(s)
Ácido Fólico/historia , Anemia/tratamiento farmacológico , Anemia/historia , Encefalopatías/etiología , Encefalopatías/historia , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/etiología , Neoplasias del Colon/historia , Femenino , Ácido Fólico/uso terapéutico , Deficiencia de Ácido Fólico/tratamiento farmacológico , Deficiencia de Ácido Fólico/historia , Historia del Siglo XX , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/historia , Metotrexato/historia , Metotrexato/uso terapéutico , Defectos del Tubo Neural/etiología , Defectos del Tubo Neural/historia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/historia , Embarazo , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Enfermedades Vasculares/etiología , Enfermedades Vasculares/historia , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/historiaRESUMEN
Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy and may be of comparatively recent, New World origin. Apart from the symptom-relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been in use since antiquity for musculoskeletal pain and inflammation, only a dozen drugs or drug classes--the disease-modifying antirheumatic drugs--are currently in common use in rheumatoid arthritis. Development of these drugs has been a notable achievement of the 20th century. Some were developed serendipitously (glucocorticoids, antimalarials), some were the product of faulty reasoning (gold, D-penicillamine), and others were applied for plausible reasons but whose mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority were originally applied on the basis of actions that remain germane to the pathophysiology of rheumatoid arthritis as currently understood (azathioprine, cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more recently introduced and effective agents. The practical use of these drugs is determined by efficacy-toxicity considerations, which have also driven the recent development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Antiinflamatorios no Esteroideos/historia , Antimaláricos/historia , Antimaláricos/uso terapéutico , Antirreumáticos/historia , Artritis Reumatoide/historia , Azatioprina/historia , Azatioprina/uso terapéutico , Glucocorticoides/historia , Glucocorticoides/uso terapéutico , Oro/historia , Oro/uso terapéutico , Historia del Siglo XX , Humanos , Metotrexato/historia , Metotrexato/uso terapéutico , Penicilamina/historia , Penicilamina/uso terapéutico , Sulfasalazina/historia , Sulfasalazina/uso terapéuticoAsunto(s)
Tetrahidrofolato Deshidrogenasa/historia , Ácido Fólico/análogos & derivados , Ácido Fólico/química , Ácido Fólico/historia , Historia del Siglo XX , Leucovorina/química , Leucovorina/historia , Metotrexato/química , Metotrexato/historia , NADP/química , NADP/historia , Tetrahidrofolato Deshidrogenasa/químicaRESUMEN
We have reviewed the treatment of rheumatoid arthritis (RA) in pertinent selected literature with a focus on methotrexate (MTX). Considerable progress has been made over the last 120 years since the introduction of salicylates to treat rheumatic symptoms. Most slow acting antirheumatic drugs became widely used in the years after the second world war. MTX became widely accepted in the 1980s although early reports of its use predate that time. The historical perspective of the development of agents to treat RA indicates that most significant advances are concentrated in the last 45 years, especially the last 15 years. This trend will likely continue.