RESUMEN
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. PATIENTS AND METHODS: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. RESULTS: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. CONCLUSIONS: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
Asunto(s)
Antígeno Ki-1 , Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Brentuximab Vedotina , Humanos , Antígeno Ki-1/metabolismo , Antígeno Ki-1/uso terapéutico , Linfoma de Células T Periférico/tratamiento farmacológico , Vincristina/efectos adversosRESUMEN
BACKGROUND: A previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak. METHODS: In order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). RESULTS: Of the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available. CONCLUSION: Off-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.
Asunto(s)
Antineoplásicos/uso terapéutico , Aprobación de Drogas , Medicina Basada en la Evidencia , Neoplasias/tratamiento farmacológico , Uso Fuera de lo Indicado/normas , Manejo de Atención al Paciente/normas , Guías de Práctica Clínica como Asunto/normas , Humanos , Neoplasias/patología , Uso Fuera de lo Indicado/legislación & jurisprudencia , Uso Fuera de lo Indicado/estadística & datos numéricos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estados Unidos , United States Food and Drug AdministrationRESUMEN
BACKGROUND: Advanced age at diagnosis is considered a poor prognostic factor in mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the outcomes and prognostic factors in patients diagnosed at an advanced age (≥65 years) with MF/SS. METHODS: Survival, progression rates and various clinical and histopathological variables were studied in a group of 174 elderly patients diagnosed with MF/SS between 1992 and 2015 at a single referral cancer center in the United States. Kaplan-Meier estimates were used to determine survival and progression and Cox proportional hazards regression univariate and multivariate models were used to identify prognostic factors. RESULTS: Of 174 elderly patients, 76.4% were diagnosed with early-stage (clinical stages IA-IIA) and 23.6% with late-stage MF/SS (IIB-IV). Advanced age was associated with poor overall survival, but not with disease-specific survival (DSS) or progression-free survival (PFS). Gender, increasing clinical stage, T and B classifications, elevated lactate dehydrogenase (LDH) levels and development of large cell transformation (LCT) were significant predictors of poor survival or disease progression. Patients with early-stage MF and <10% total skin involvement (T1 classification) or patch-only disease (T1a/T2a) showed better PFS with no observed disease-specific mortality. Folliculotropic MF was associated with poor DSS in patients with early-stage disease. CONCLUSIONS: Older age at diagnosis of MF/SS does not predict worse disease-specific outcomes. Elderly patients with early-stage disease, specifically involving less than 10% of the skin surface with patches but without plaques or folliculotropism, have an excellent prognosis. However, the development of LCT is a strong prognostic indicator of poor survival in elderly patients with MF/SS.
Asunto(s)
Micosis Fungoide/patología , Síndrome de Sézary/patología , Neoplasias Cutáneas/patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , L-Lactato Deshidrogenasa/sangre , Masculino , Estadificación de Neoplasias , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores Sexuales , Tasa de SupervivenciaRESUMEN
Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.
Asunto(s)
Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/psicología , Hijo de Padres Discapacitados/psicología , Imagen de Difusión por Resonancia Magnética/tendencias , Adolescente , Trastorno Bipolar/genética , Niño , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Masculino , Psicopatología , Factores de RiesgoAsunto(s)
Inmunoconjugados , Antígeno Ki-1 , Brentuximab Vedotina , Enfermedad de Hodgkin , Humanos , Linfoma FolicularRESUMEN
BACKGROUND: Advanced-stage mycosis fungoides (MF)/Sézary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. PATIENTS AND METHODS: This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). RESULTS: Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. CONCLUSION: This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach.
Asunto(s)
Micosis Fungoide/terapia , Síndrome de Sézary/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Brasil/epidemiología , Niño , Europa (Continente)/epidemiología , Femenino , Humanos , Japón/epidemiología , Masculino , Oncología Médica/métodos , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Micosis Fungoide/mortalidad , Micosis Fungoide/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Síndrome de Sézary/mortalidad , Síndrome de Sézary/patología , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. METHOD: LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. RESULTS: Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. CONCLUSIONS: These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.
Asunto(s)
Conducta del Adolescente/fisiología , Síntomas Afectivos/fisiopatología , Corteza Cerebral , Depresión/fisiopatología , Problema de Conducta , Recompensa , Trastornos Relacionados con Sustancias/diagnóstico , Adolescente , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiología , Corteza Cerebral/fisiopatología , Niño , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Trastornos Relacionados con Sustancias/diagnóstico por imagen , Trastornos Relacionados con Sustancias/patología , Trastornos Relacionados con Sustancias/fisiopatologíaRESUMEN
Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.
Asunto(s)
Síntomas Afectivos/fisiopatología , Sustancia Blanca/fisiopatología , Adolescente , Síntomas Afectivos/genética , Trastorno Bipolar/diagnóstico , Encéfalo/fisiopatología , Niño , Emociones/fisiología , Femenino , Predicción/métodos , Humanos , Estudios Longitudinales , Masculino , Padres/psicología , Escalas de Valoración Psiquiátrica , Recompensa , Resultado del TratamientoRESUMEN
BACKGROUND: For patients with peripheral T-cell lymphoma (PTCL), the value of (18)fluoro-deoxyglucose positron emission tomography (FDG-PET) scans for assessing prognosis and response to treatment remains unclear. The utility of FDG-PET, in addition to conventional radiology, was examined as a planned exploratory end point in the pivotal phase 2 trial of romidepsin for the treatment of relapsed/refractory PTCL. PATIENTS AND METHODS: Patients received romidepsin at a dose of 14 mg/m(2) on days 1, 8, and 15 of 28-day cycles. The primary end point was the rate of confirmed/unconfirmed complete response (CR/CRu) as assessed by International Workshop Criteria (IWC) using conventional radiology. For the exploratory PET end point, patients with at least baseline FDG-PET scans were assessed by IWC + PET criteria. RESULTS: Of 130 patients, 110 had baseline FDG-PET scans, and 105 were PET positive at baseline. The use of IWC + PET criteria increased the objective response rate to 30% compared with 26% by conventional radiology. Durations of response were well differentiated by both conventional radiology response criteria [CR/CRu versus partial response (PR), P = 0.0001] and PET status (negative versus positive, P < 0.0001). Patients who achieved CR/CRu had prolonged progression-free survival (PFS, median 25.9 months) compared with other response groups (P = 0.0007). Patients who achieved PR or stable disease (SD) had similar PFS (median 7.2 and 6.3 months, respectively, P = 0.6427). When grouping PR and SD patients by PET status, patients with PET-negative versus PET-positive disease had a median PFS of 18.2 versus 7.1 months (P = 0.0923). CONCLUSIONS: Routine use of FDG-PET does not obviate conventional staging, but may aid in determining prognosis and refine response assessments for patients with PTCL, particularly for those who do not achieve CR/CRu by conventional staging. The optimal way to incorporate FDG-PET scans for patients with PTCL remains to be determined. TRIAL REGISTRATION: NCT00426764.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Depsipéptidos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Fluorodesoxiglucosa F18/farmacocinética , Linfoma de Células T Periférico/diagnóstico por imagen , Tomografía de Emisión de Positrones/estadística & datos numéricos , Estudios de Seguimiento , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/mortalidad , Linfoma de Células T Periférico/patología , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Radiofármacos/farmacocinética , Inducción de Remisión , Tasa de Supervivencia , Distribución TisularRESUMEN
BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.
Asunto(s)
Desarrollo del Adolescente/fisiología , Síntomas Afectivos/fisiopatología , Amígdala del Cerebelo/fisiopatología , Síntomas Conductuales/fisiopatología , Corteza Prefrontal/fisiopatología , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: High response rates for doxorubicin HCl liposome injection (DLI) in cutaneous T-cell lymphoma (CTCL) have been reported with vague criteria until recently. Approximately 50% of CTCL patients respond to bexarotene (Bex). PATIENTS AND METHODS: A phase II trial was carried out to clarify the true overall response rate (ORR) for DLI and to assess the role of sequential Bex. Patients were treated with DLI 20 mg/m(2) i.v. every 2 weeks for 16 weeks (8 doses) followed by 16 weeks with Bex 300 mg/m(2) orally. Response assessments were carried out after 16 (DLI) and 32 weeks (Bex). Skin responses were measured by the modified Severity-Weighted Assessment Tool (mSWAT) and the Composite Assessment of Index Lesion Severity (CA). RESULTS: Thirty-seven patients were treated: stage IV (22, 8 with Sézary syndrome), IIB (10), earlier stage refractory to skin-directed therapies or radiation therapy (5). For 34 assessable patients: ORR 14/34 [41%: partial response (PR) 12, clinical complete response (CCR) 2]. Maximum responses were all seen after 16 weeks DLI. Median progression-free survival (PFS) was 5 months. There were 22 deaths: 21 of disease and 1 of heart failure. Twenty-seven grade 3 and 5 grade 4 toxic events were observed. CONCLUSION(S): With strict criteria, DLI ORR is among the highest reported for single agents in CTCL. Sequential Bex did not increase the response rate or duration.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma Cutáneo de Células T/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Bexaroteno , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Inyecciones , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Neoplasias Cutáneas/mortalidad , Tetrahidronaftalenos/administración & dosificación , Resultado del TratamientoRESUMEN
Hyperpigmentation has traditionally been a relatively difficult condition to treat, especially in darker racial ethnic groups. Multiple topical agents available act upon different steps of the pigmentation pathway. We review these topical agents, their mechanisms of action, and their effectiveness as monotherapy and in combination with other compounds. Ultimately, combination therapy is the most efficacious when considering overall depigmentation as well as treatment time required to achieve clinical improvement.
Asunto(s)
Hiperpigmentación/tratamiento farmacológico , Preparaciones para Aclaramiento de la Piel/administración & dosificación , Quimioterapia Combinada , Humanos , Hidroquinonas/administración & dosificación , Hiperpigmentación/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Hyperpigmentation has traditionally been a relatively difficult condition to treat, especially in darker racial ethnic groups. Multiple topical agents available act upon different steps of the pigmentation pathway. We review these topical agents, their mechanisms of action, and their effectiveness as monotherapy and in combination with other compounds. Ultimately, combination therapy is the most efficacious when considering overall depigmentation as well as treatment time required to achieve clinical improvement.
Asunto(s)
Hiperpigmentación/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Preparaciones para Aclaramiento de la Piel/uso terapéutico , Administración Tópica , Corticoesteroides/administración & dosificación , Arbutina/administración & dosificación , Arbutina/uso terapéutico , Cromonas/administración & dosificación , Cromonas/uso terapéutico , Combinación de Medicamentos , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/uso terapéutico , Glucósidos/administración & dosificación , Glucósidos/uso terapéutico , Humanos , Hidroquinonas/uso terapéutico , Queratolíticos/administración & dosificación , Queratolíticos/uso terapéutico , Monofenol Monooxigenasa/antagonistas & inhibidores , Niacinamida/administración & dosificación , Niacinamida/uso terapéutico , Fitoterapia , Preparaciones de Plantas/administración & dosificación , Preparaciones de Plantas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor PAR-2/antagonistas & inhibidores , Retinoides/administración & dosificación , Retinoides/uso terapéutico , Preparaciones para Aclaramiento de la Piel/administración & dosificación , Pigmentación de la Piel/efectos de los fármacosRESUMEN
The purpose of this study was to assess the inter-rater reliability of the P-TRI, a 17-item instrument developed to identify risk factors associated with poor treatment adherence in pediatric solid organ transplant candidates. Because factors influencing treatment adherence may vary with age, the 89 subject samples were divided into pre-adolescent (0-11 yr) and adolescent (12-19 yr) groups. Each subject received two independent P-TRI ratings based on pretransplant psychosocial assessments separately conducted by a PSYC and a SWTC. Inter-rater reliability was assessed using the delta statistic. Overall, agreement was higher in the pre-adolescent group, with delta>0.70 for five items and delta<0.30 for two items. For the adolescent group, one item had a delta>0.70 and seven items had a delta<0.30. Overall, PSYC P-TRI ratings indicated fewer areas of concern on items assessing family dynamics compared with SWTC P-TRI ratings, whereas the reverse was true for items related to psychiatric history. Results highlight the challenges of conducting a reliable pretransplant assessment of adherence-related risk factors and suggest the need for revisions to the P-TRI prior to its use in clinical practice.
Asunto(s)
Protección a la Infancia , Adhesión a Directriz , Trasplante de Órganos/normas , Selección de Paciente , Obtención de Tejidos y Órganos/organización & administración , Adolescente , California , Niño , Preescolar , Estudios de Cohortes , Comunicación , Femenino , Indicadores de Salud , Humanos , Lactante , Masculino , Variaciones Dependientes del Observador , Trasplante de Órganos/psicología , Relaciones Padres-Hijo , Cooperación del Paciente/estadística & datos numéricos , Cuidados Preoperatorios/normas , Cuidados Preoperatorios/tendencias , Relaciones Profesional-Familia , Psicometría , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B(12) might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B(12) administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B(12) pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.