RESUMEN
5-fluorouracil (5-FU) and 5-FU derivatives, such as capecitabine, UFT, and S-1, are the mainstay of chemotherapy treatment for gastrointestinal cancers, and other solid tumors. Compared with other cytotoxic chemotherapies, these drugs generally have a favorable safety profile, but hematologic and gastrointestinal toxicities remain common. DFP-11207 is a novel oral cytotoxic agent that combines a 5-FU pro-drug with a reversible DPD inhibitor and a potent inhibitor of OPRT, resulting in enhanced pharmacological activity of 5-FU with decreased gastrointestinal and myelosuppressive toxicities. In this Phase I study (NCT02171221), DFP-11207 was administered orally daily, in doses escalating from 40 mg/m2/day to 400 mg/m2/day in patients with esophageal, colorectal, gastric, pancreatic or gallbladder cancer (n = 23). It was determined that DFP-11207 at the dose of 330 mg/m2/day administered every 12 hours was well-tolerated with mild myelosuppressive and gastrointestinal toxicities. The pharmacokinetic analysis determined that the 5-FU levels were in the therapeutic range at this dose. In addition, fasted or fed states had no influence on the 5-FU levels (patients serving as their own controls). Among 21 efficacy evaluable patients, 7 patients had stable disease (33.3%), of which two had prolonged stable disease of >6 months duration. DFP-11207 can be explored as monotherapy or easily substitute 5-FU, capecitabine, or S-1 in combination regimens.
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Antimetabolitos Antineoplásicos/administración & dosificación , Hidrocarburos Fluorados/administración & dosificación , Neoplasias/tratamiento farmacológico , Profármacos/administración & dosificación , Pirimidinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/farmacocinética , Área Bajo la Curva , Femenino , Fluorouracilo/sangre , Interacciones Alimento-Droga , Humanos , Hidrocarburos Fluorados/efectos adversos , Hidrocarburos Fluorados/farmacocinética , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/metabolismo , Profármacos/efectos adversos , Profármacos/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Resultado del TratamientoRESUMEN
BACKGROUND: DFP-10917, a deoxycytidine nucleoside analogue, has a unique mechanism of action resulting in leukemic cell death when administered for prolonged periods at low doses. The current phase 1/2 study investigated the safety, maximum tolerated dose, and evidence of antileukemic activity for DFP-10917 administered by 7-day or 14-day continuous intravenous infusion in patients with recurrent or refractory acute myeloid leukemia (AML). METHODS: In the phase 1 dose escalation portion of the study, patients were administered DFP-10917 by 7-day continuous intravenous infusion plus 21-day rest (stage 1) or 14-day continuous intravenous infusion plus 14-day rest (stage 2). The primary objectives of phase 1 were to determine the maximum tolerated dose, the phase 2 dose, and the dose-limiting toxicities (DLTs) of DFP-10917. The primary objectives of phase 2 were to evaluate the overall response rate of DFP-10917 using complete response (CR), CR without platelet recovery (CRp), CR with incomplete blood count recovery (CRi) or partial response. RESULTS: In stage 1 of phase 1 (4-35 mg/m2 /day as a 7-day continuous intravenous infusion), a DLT of grade 3 diarrhea occurred at a dose of 35 mg/m2 /day. In stage 2 of phase 1, a dose of 10 mg/m2 /day as a 14-day continuous intravenous infusion resulted in DLTs of prolonged hypocellularity, abdominal pain, diarrhea, and vomiting. The dose of 6 mg/m2 /day as a 14-day continuous intravenous infusion was found to be well tolerated and was selected for phase 2. Response rates in patients in phase 2 (N = 29) were 20.7% CR, 3.4% CRp, and 24.1% CRi. The overall response rate was 48.3% (95% confidence interval, 29.4%-67.5%). CONCLUSIONS: DFP-10917 as a 14-day continuous intravenous infusion at a dose of 6 mg/m2 /day can be administered safely and appears to be effective in patients with recurrent or refractory AML. A phase 3 investigation comparing DFP-10917 monotherapy versus standard of care in an early recurrent or refractory AML setting is warranted.
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Desoxicitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Desoxicitidina/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/diagnóstico , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Recurrencia , Inducción de Remisión , Medición de Riesgo , Terapia Recuperativa , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Integrated assessment models offer a crucial support to decisionmakers in climate policy making. For a full understanding and corroboration of model results, analysts ought to identify the exogenous variables that influence the model results the most (key drivers), appraise the relevance of interactions, and the direction of change associated with the simultaneous variation of uncertain variables. We show that such information can be directly extracted from the data set produced by Monte Carlo simulations. Our discussion is guided by the application to the well-known DICE model of William Nordhaus. The proposed methodology allows analysts to draw robust insights into the dependence of future atmospheric temperature, global emissions, and carbon costs and taxes on the model's exogenous variables.
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Cambio Climático , Modelos Teóricos , Medición de Riesgo/métodos , Incertidumbre , Simulación por Computador , Método de MontecarloRESUMEN
BACKGROUND: Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma. METHODS: Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis. RESULTS: A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P=0.01) and overall survival (86±4% vs. 75±5% at 2 years, P=0.02 without adjustment for interim analyses). CONCLUSIONS: Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma. (Funded by the National Institutes of Health and the Food and Drug Administration; ClinicalTrials.gov number, NCT00026312.)
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Anticuerpos Monoclonales/uso terapéutico , Gangliósidos/inmunología , Inmunoterapia , Neuroblastoma/terapia , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/uso terapéutico , Niño , Preescolar , Terapia Combinada , Quimioterapia Combinada , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Inmunoterapia/efectos adversos , Lactante , Análisis de Intención de Tratar , Interleucina-2/uso terapéutico , Isotretinoína/uso terapéutico , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/mortalidad , Trasplante de Células Madre , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To better understand and compare resident family and nursing home staff experiences and perceptions of licensed and unlicensed direct care staff turnover. DESIGN: Descriptive qualitative design. SETTING AND PARTICIPANTS: Nursing home resident family members and direct care registered nurses (RNs), licensed practical nurses (LPNs), certified nursing assistants (CNAs), and administrative staff. METHODS: We conducted semistructured interviews with family members and nursing home staff between September 2019 and July 2020. Using a rapid analysis approach, we compared family member, direct care RNs, LPNs, CNAs, and administrative staff experiences and perceptions related to staff turnover, ways to reduce turnover, and strategies for minimizing disruptions. RESULTS: We completed interviews with 17 family members, 25 direct care RNs, LPNs, and CNAs, and 6 administrative staff from 13 nursing homes primarily located in southeastern Michigan. Family members had mixed experiences with turnover, but commonly described the need for consistent, personalized care to ensure safe, high-quality resident care. Direct care RNs, LPNs, and CNAs expressed a similar viewpoint and frustration with not being able to provide the care they would like because of turnover or short staffing. Although better wages were mentioned, all groups also identified the importance of staff feeling appreciated and supported as critical for decreasing turnover. Adequate training and strategies to acclimate new staff to resident preferences were also noted as approaches for minimizing care disruptions during turnover. CONCLUSIONS AND IMPLICATIONS: Our findings largely confirm those of others regarding potential contributing factors and consequences of staff turnover. However, our findings also provide a clear message about important areas on which to focus. This includes identifying ways to effectively provide consistent, person-centered care for residents in the context of staffing inconsistencies and the need for a more people-oriented work environment for nursing home staff to reduce turnover and minimize disruptions in resident care.
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Asistentes de Enfermería , Personal de Enfermería , Humanos , Casas de Salud , Reorganización del Personal , Investigación CualitativaRESUMEN
This paper calls attention to design features that could enhance the helpfulness of the decision table to decision makers trying to get a better intuitive grasp of the choices facing them. The experiments reported here show that the grey scale is more facilitative than the number scale for problem comprehension as measured by the identification of dominance and the identification of non-additivity, each of which requires a view of the decision problem that is sensitive to patterns across attributes. Additional design features that could enhance the decision makers' grasp of the choices facing them are suggested for further research.
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Toma de Decisiones/fisiología , Técnicas de Apoyo para la Decisión , Percepción Visual/fisiología , Muñones de Amputación/fisiopatología , Estudios Cruzados , Femenino , Humanos , Masculino , Dolor/fisiopatología , Estimulación Luminosa , Estadísticas no Paramétricas , Estudiantes , UniversidadesRESUMEN
PURPOSE: The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. PATIENTS AND METHODS: We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. RESULTS: A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. CONCLUSIONS: When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials.
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Antineoplásicos/administración & dosificación , Bortezomib/administración & dosificación , Ensayos Clínicos como Asunto/métodos , Cálculo de Dosificación de Drogas , Neoplasias/tratamiento farmacológico , Inhibidores de Proteasoma/administración & dosificación , Proyectos de Investigación , Antineoplásicos/efectos adversos , Bortezomib/efectos adversos , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Dosis Máxima Tolerada , Terapia Molecular Dirigida , Neoplasias/enzimología , Neoplasias/patología , Modelos de Riesgos Proporcionales , Inhibidores de Proteasoma/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.
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Neoplasias/diagnóstico , Neoplasias/terapia , Selección de Paciente/ética , Experimentación Humana Terapéutica/ética , Niño , Preescolar , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Femenino , Terapia Genética/métodos , Directrices para la Planificación en Salud , Humanos , Masculino , Medición de Riesgo , Conservación de Tejido , Estados UnidosRESUMEN
Childhood osteogenic sarcoma (OS) is a rare bone cancer occurring primarily in adolescents. The North American pediatric cooperative groups have performed a series of clinical treatment trials in this disease over the past several decades, and biology studies of tumor tissue have been an important study component. A meeting was held in Bethesda, Maryland on November 29-30, 2001, sponsored by the NIH Office of Rare Diseases, the Children's Oncology Group, and the National Cancer Institute-Cancer Therapy Evaluation Program with the general objectives: (a) to review the current state of knowledge regarding OS biology; (b) to identify, prioritize, and support the development of biology studies of potential clinical relevance in OS; and (c) to discuss the available tissue resources and the appropriate methods for analysis of OS samples for the conduct of biology studies. This report summarizes the information presented and discussed by the meeting participants.
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Neoplasias Óseas/fisiopatología , Osteosarcoma/fisiopatología , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Niño , Humanos , Neovascularización Patológica/prevención & control , Osteosarcoma/genética , Osteosarcoma/patología , Osteosarcoma/terapiaRESUMEN
Recent progress in establishing a European network to conduct paediatric oncology phase I/II clinical trials calls attention to the challenges facing researchers developing new agents for children with cancer. These challenges include: ensuring that effective infrastructures are in place to safely and efficiently conduct early phase clinical trials in children while meeting all ethical and regulatory requirements associated with such trials; obtaining timely access to new agents from pharmaceutical sponsors for both preclinical testing and for phase I and phase II testing; and effectively prioritizing new agents for evaluation in children so that those agents most likely to benefit children with specific cancers are brought forward for clinical testing. The use of public funds to develop and maintain clinical trials infrastructures devoted to paediatric oncology drug development can help in addressing these challenges and can facilitate the timely paediatric evaluation of new agents, thereby contributing to the goal of identifying more effective treatments for children with cancer.
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Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Niño , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Europa (Continente) , Humanos , Cooperación Internacional , Estudios Multicéntricos como AsuntoRESUMEN
OBJECTIVE: To compare the effects of administering propofol as a continuous infusion vs. bolus dosing in children undergoing ambulatory oncologic procedures in the pediatric intensive care unit (PICU). DESIGN: Prospective, randomized study. SETTING: Tertiary PICU in a university hospital. PATIENTS: Ambulatory oncology patients scheduled for diagnostic or therapeutic procedures with propofol anesthesia in the PICU were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive either continuous infusion or bolus administration of propofol in a protocol-driven manner. All patients received an initial bolus of 1.5 mg/kg, with additional 0.5 mg/kg doses until complete induction. Continuous infusions were started at 0.1 mg/kg/min and, if needed, increased 20% after a bolus of 0.5 mg/kg. Bolus group patients were given doses of 0.5 mg/kg if needed. Ramsay scores of < 5 were used as criteria for additional dosing. MEASUREMENTS AND MAIN RESULTS: Eighteen patients undergoing 40 separate procedures were enrolled during the study period. Twenty procedures each were performed with continuous or bolus administration of propofol. No differences were present between groups in demographic characteristics, induction dose and time, procedure and recovery times, or adverse events. All patients had adequate anesthesia and favorable satisfaction scores. More boluses were needed in the bolus group (8.5 +/- 4.6 vs. 5.4 +/- 2.9; p < .05). Average systolic blood pressure decreased more in the continuous infusion group (26.4% +/- 12 vs. 19.3% +/- 10; p < .05). Total propofol dose was higher in the continuous infusion group (8.0 mg/kg +/- 3.8 vs. 5.7 mg/kg +/- 2.4; p < .05). CONCLUSION: Both continuous and bolus administration of propofol provided conditions for conducting oncologic procedures that were satisfying to patients, their families, and physicians. Continuous infusions were associated with a larger total dose and greater decreases in systolic blood pressure. Physician preference is likely to dictate which method is used.
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Anestesia Intravenosa , Anestésicos Intravenosos/administración & dosificación , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Propofol/administración & dosificación , Adolescente , Adulto , Atención Ambulatoria , Antineoplásicos/administración & dosificación , Biopsia con Aguja , Catéteres de Permanencia , Niño , Preescolar , Femenino , Humanos , Lactante , Infusiones Intravenosas , Inyecciones Intravenosas , Unidades de Cuidado Intensivo Pediátrico , Masculino , Estudios Prospectivos , Punción Espinal , Resultado del TratamientoAsunto(s)
Actitud del Personal de Salud , Ensayos Clínicos como Asunto , Oncología Médica , Médicos/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto , Humanos , Pediatría , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Estados Unidos , Recursos HumanosAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos como Asunto , Derivación y Consulta , Rabdomiosarcoma/terapia , Niño , Preescolar , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Ensayos Clínicos Fase III como Asunto , Humanos , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos como Asunto , Niño , Protección a la Infancia , Germinoma/tratamiento farmacológico , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Retinoblastoma/tratamiento farmacológico , Sarcoma/tratamiento farmacológicoAsunto(s)
Ensayos Clínicos como Asunto , Neuroblastoma/terapia , Adolescente , Adulto , Niño , Preescolar , Recursos en Salud , Humanos , Lactante , Recién Nacido , Derivación y ConsultaRESUMEN
One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.
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Neoplasias/patología , Adolescente , Adulto , HumanosRESUMEN
Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success in curing children with cancer.
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Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Cardiomiopatías/tratamiento farmacológico , Fármacos Cardiovasculares/uso terapéutico , Neoplasias/tratamiento farmacológico , Razoxano/uso terapéutico , Cardiomiopatías/inducido químicamente , Niño , HumanosRESUMEN
BACKGROUND: The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials. PROCEDURE: Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m2/day on day 0-4), carboplatin (400 mg/m2/day on day 0-1), etoposide (100 mg/m2/day on day 0-4) and either rhG-CSF (10 microg/kg/day vs. 5 microg/kg/day, CCG-0894, 71 patients), PIXY321 (500-1,000 microg/m2/day, CCG-0924, 14 patients), or rhG-CSF (5 microg/kg/day) and IL-6 (2.5-5 microg/kg/day, CCG-0931, 12 patients). RESULTS: Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.8-22.5 years). Tumor types were osteosarcoma (OTS) (n = 34), rhabdomyosarcoma (n = 27), Ewing sarcoma (EWS) (n = 21), soft tissue sarcoma-not otherwise specified (n = 5), undifferentiated sarcoma (n = 6), fibrosarcoma (n = 2), peripheral primitive neuroectodermal tumor (n = 1), and extraosseous Ewing (n = 1). The ORR was 51% (27% complete response [CR]). OS at 1 and 2 years was 49% and 28%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P < 0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P < 0.005). CONCLUSIONS: The ORR to ICE reinduction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Sarcoma/tratamiento farmacológico , Adolescente , Adulto , Carboplatino/administración & dosificación , Niño , Preescolar , Factores Estimulantes de Colonias/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , Rabdomiosarcoma/tratamiento farmacológico , Rabdomiosarcoma/mortalidad , Sarcoma/mortalidad , Tasa de SupervivenciaRESUMEN
The presence of scolopophorous organs in aquatic Heteroptera has been reported in a number of species. This study presents a morphological investigation of these sensory structures of Lethocerus (Belostomatidae) as observed with the scanning electron microscope (SEM). Paired mesothoracic and metathoracic organs are present. Externally, each sensory structure consists of a raised sensory membrane. The distal-most portion consists of thickenings of this sensory membrane (sclerite). The receptor neurons of the mesothoracic organ are of two types-one discolopidial sensillum and 12 monoscolopidial sensilla. The former is attached to the internal wall and distal thickening of the sensory membrane, while the latter are dispersed throughout the interior and attached to the internal wall of the sensory membrane. The structure of the organs suggest that an effective stimulus could be a compression of the membrane. A discussion of possible functions (pressure reception and hearing) is included.