RESUMEN
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/historiaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/historia , Quimioterapia de Inducción/historia , Quimioterapia de Inducción/métodos , Oncología Médica/historia , Pediatría/historia , Leucemia-Linfoma Linfoblástico de Células Precursoras/historia , Asparaginasa/historia , Niño , Ciclofosfamida/historia , Citarabina/historia , Dexametasona/historia , Doxorrubicina/historia , Alemania , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Tioguanina/historia , Vincristina/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/historiaAsunto(s)
Traslado Adoptivo/historia , Ciclofosfamida/historia , Inmunoterapia/historia , Leucemia/historia , Leucemia/terapia , Traslado Adoptivo/métodos , Animales , Ciclofosfamida/uso terapéutico , Historia del Siglo XX , Humanos , Inmunoterapia/métodos , Ratones , Linfocitos T/inmunología , Trasplante Isogénico , Resultado del TratamientoRESUMEN
This paper reviews the development of therapy for acute myelogenous leukemia that in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early 1970s is reviewed, the discovery of the two drugs in question described, and the introduction of clinical trials to reach an optimal regimen for their use delineated. During the 1950s, following World War Two and after a period of civil reconstitution, a national effort, facilitated by the U.S. Congress and federal investments in the National Cancer Institute, was initiated to enhance cancer therapy in the United States. The development of mouse models of leukemia and advances in understanding the structure and function of DNA and RNA and the process of cell proliferation provided new targets for drug development and new concepts for their use. The year, 2013, marks the 40th year that this protocol, 7+3, is the method of induction of remission for most patients with acute myelogenous leukemia. Its inadequacies also are made clear. Many patients with the disease die soon after diagnosis, and patients who have more unfavorable oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance to therapy make up the vast majority of the affected and few are cured. It is evident to all that new paradigms are needed if acute myelogenous leukemia is to be subdued in most patients with the disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/historia , Hematología/historia , Leucemia Mieloide Aguda/tratamiento farmacológico , Oncología Médica/historia , Adolescente , Adulto , Anciano , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Instituciones Oncológicas/historia , Manejo de Caso/historia , Niño , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/historia , Ciclofosfamida/aislamiento & purificación , Ciclofosfamida/farmacología , Citarabina/administración & dosificación , Citarabina/efectos adversos , Citarabina/historia , Citarabina/aislamiento & purificación , Citarabina/farmacología , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Daunorrubicina/historia , Daunorrubicina/aislamiento & purificación , Daunorrubicina/farmacología , Perros , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Predicción , Francia , Haplorrinos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Masculino , Mercaptopurina/administración & dosificación , Mercaptopurina/efectos adversos , Mercaptopurina/historia , Mercaptopurina/aislamiento & purificación , Mercaptopurina/farmacología , Persona de Mediana Edad , National Institutes of Health (U.S.)/historia , Ratas , Inducción de Remisión , Estados UnidosRESUMEN
The introduction of cyclophosphamide (CyP) as a treatment for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) has been among the most significant contributions in vasculitis. Prior to the introduction of CyP, WG was a uniformly fatal disease, with mortality occurring within 5-12 months from pulmonary or renal failure or from infection due to glucocorticoids. In 1973 Fauci and Wolff, at the National Institutes of Health, published their experience with a regimen that combined CyP and prednisone in which disease remission was seen in 12 of 14 patients. Long-term experience with CyP provided even greater evidence for its efficacy in which an 80% survival rate was seen, with 91% of patients having significant improvement and 75% achieving complete remission. However, extended follow-up also demonstrated that disease relapse occurred in at least 50% of patients and that 42% experienced morbidity solely as a result of treatment. These observations showed that while CyP was life-saving, it did not prevent relapse and was associated with significant toxicity such that safer means to induce remission needed to be pursued. Strategies aimed at reducing exposure to CyP have included intermittent administration, induction-maintenance regimens and avoidance of CyP for non-severe disease. Recently, the introduction of rituximab has raised important questions regarding the place of CyP in the treatment of WG/MPA. This paper examines the past, present and future of CyP through a review of its efficacy and safety.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Granulomatosis con Poliangitis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Poliangitis Microscópica/tratamiento farmacológico , Prednisona/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Ciclofosfamida/efectos adversos , Ciclofosfamida/historia , Femenino , Granulomatosis con Poliangitis/mortalidad , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Inmunosupresores/efectos adversos , Masculino , Poliangitis Microscópica/mortalidad , Prednisona/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Inducción de Remisión , Rituximab , Resultado del TratamientoAsunto(s)
Antineoplásicos Alquilantes/historia , Ciclofosfamida/historia , Neoplasias Mamarias Animales/historia , Animales , Antineoplásicos Alquilantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Historia del Siglo XX , Neoplasias Mamarias Animales/tratamiento farmacológico , Neoplasias Mamarias Animales/cirugía , Ratones , Ratones EndogámicosRESUMEN
In this overview of the pharmacology of the anticancer drug cyclophosphamide, a brief history of the development of this drug from the general class of nitrogen mustards is provided. The antitumor activity of cyclophosphamide and its isomer ifosfamide is discussed through considerations of metabolism, resistance, detoxification, and DNA cross-linking. Clinical uses in general chemotherapy, bone marrow transplantation and immunosuppression are presented. A review with 73 references.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Ciclofosfamida/uso terapéutico , Inmunosupresores/uso terapéutico , Antineoplásicos Alquilantes/historia , Antineoplásicos Alquilantes/farmacología , Ciclofosfamida/historia , Ciclofosfamida/farmacología , Historia del Siglo XX , Humanos , Inmunosupresores/historia , Inmunosupresores/farmacologíaRESUMEN
Cyclophosphamide (CP) has been in clinical use for the treatment of malignant disease for over 40 years. CP is inactive until it undergoes complex metabolic pathways leading to the ultimate alkylating agent, phosphoramide mustard, but also to inactive and toxic metabolites. Sensitive and specific methods are now available for the measurement of CP and its enantiomers, its metabolites and their stereoisomers, in biological matrices. An overview is given of the methods of analysis of CP and its metabolites described in literature since 1993 as well as the current knowledge about its metabolism. Five classes of methods are described: (1) thin-layer chromatography-photographic densitometry, (2) high performance liquid chromatography, (3) gas chromatography and gas chromatography coupled to mass spectrometry, (4) phosphorus-31 nuclear magnetic resonance and (5) enantiomeric separation. In each case, sample clean up and preparation are described. Precision and limits of quantification of the assays are indicated. A table summarizes all the analytical methods for assaying each metabolite.