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1.
BMJ Support Palliat Care ; 13(e1): e156-e162, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33122168

RESUMEN

OBJECTIVES: More than 50% patients develop emesis during induction therapy for acute myeloid leukaemia (AML). The addition of aprepitant for emesis control in children receiving induction for AML have not been explored. METHODS: A single-institutional randomised, open-label trial (NCT02979548) was conducted where children between 5 and 18 years with the diagnosis of AML being planned for 3+7 induction regimen were included. All study participants received ondansetron (0.15 mg/kg) every 8 hours for 8 days starting 30 min prior to chemotherapy. Children belonging to aprepitant group additionally received aprepitant capsules (15-40 kg=days 1-3, 80 mg; >40 kg=day 1, 125 mg and days 2-3, 80 mg) starting from 1 hour prior to chemotherapy. The proportion of patients with complete response (CR) in chemotherapy induced vomiting (CIV) in acute phase (day 1-8), delayed phase (day 9-13), overall and initial 96 hours were recorded along with severity of vomiting and adverse effects. RESULTS: Total 78 children were randomised (Aprepitant group: 37 and control group: 41). The proportion of patients with CR in CIV was significantly higher in Aprepitant group in acute phase (p=0.007), overall phase (p=0.007) and in initial 96 hours (p<0.001) but it was not different in delayed phase (p=0.07). The first episode of vomiting was also significantly delayed in aprepitant group (p=0.02). Adverse effect profile was similar in two groups. CONCLUSION: Aprepitant significantly improves emesis control in children receiving induction therapy for AML, especially in acute phase and should be routinely incorporated as part of antiemetic prophylaxis. TRIAL REGISTRATION NUMBER: The study was registered at ClinicalTrials.gov (NCT02979548).


Asunto(s)
Antieméticos , Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Leucemia Mieloide Aguda , Humanos , Niño , Adolescente , Aprepitant/uso terapéutico , Quimioterapia de Inducción/efectos adversos , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Morfolinas/uso terapéutico , Vómitos/inducido químicamente , Vómitos/tratamiento farmacológico , Vómitos/prevención & control , Antieméticos/uso terapéutico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Enfermedad Aguda , Antineoplásicos/efectos adversos , Dexametasona/efectos adversos
2.
BMJ Support Palliat Care ; 13(2): 234-237, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33468507

RESUMEN

OBJECTIVE: Health-related quality of life (HRQoL) is an important outcome for paediatric cancer studies. We compared the HRQoL between patients of progressive paediatric solid tumours randomised to metronomic chemotherapy versus placebo. METHODS: In this double-blinded, placebo-controlled randomised study of 108 children with progressive malignancies, HRQoL was evaluated using the PedsQOL Cancer module V.3 at baseline (A1), A2 (9 weeks or earlier if progressed) or A3 (18 weeks or earlier if progressed). RESULTS: There was no statistically significant difference in the change in quality of life produced by each arm from A1 to A2 in either mean total scores or individual domain scores, reported by children or their parents. On analysing the response according to the minimal clinically important difference, defined as an improvement by 4.5 points, we found no significant differences, be it among bone-sarcomas, other tumours, responders (those who received ≥9 weeks of treatment) or non-responders. CONCLUSIONS: The present study concludes that there was no significant difference in HRQoL, between the patients in the two arms at second and later assessments. This is consistent with the other survival endpoints in the study. TRIAL REGISTRATION NUMBER: Clinical trial registration: clinicaltrials.gov Identifier: NCT01858571.


Asunto(s)
Neoplasias , Calidad de Vida , Humanos , Niño , Neoplasias/tratamiento farmacológico
3.
Clin Nutr ; 41(7): 1501-1511, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35667266

RESUMEN

BACKGROUND & AIMS: Impact of micronutrient deficiency on childhood malignancy is unexplored. We estimated the prevalence of baseline micronutrient deficiency in children with cancer and its impact on event-free survival (EFS) and overall survival (OS). METHODS: A longitudinal cohort study was conducted at a tertiary cancer centre in India. Children (≤18 years) with de novo malignancy were enrolled between October 2012 and May 2014. Baseline levels of vitamin B12, folate, zinc, selenium, copper, and iron were measured and values below 150 pmol/L, 6 ng/mL, International Zinc Nutrition Collaborative Group cut-off, 0.5 µmol/L, 10 µmol/L, and 50 µg/dL, respectively, indicated deficiency. RESULTS: Total 535 children [326 (60.9%) haematological and 209 (39.1%) solid malignancies] were enrolled with median follow-up of 66 months. Vitamin B12, folate, zinc, selenium, copper and iron deficiencies were found in 209 (39.1%), 89 (16.6%), 173 (32.3%), 39 (7.3%), 12 (2.2%), and 231 (43.2%) children, respectively. Selenium deficiency independently predicted poor EFS (hazard ratio [HR] = 1.56; p = 0.038) and OS (HR = 1.65; p = 0.027) in the cohort. In haematological malignancies, selenium deficiency predicted poor EFS (HR = 1.81; p = 0.023) and OS (HR = 2.12; p = 0.004). In solid malignancies, vitamin B12 (HR = 1.55; p = 0.028) and zinc (HR = 1.74; p = 0.009) deficiencies predicted poor EFS, and zinc deficiency predicted poor OS (HR = 1.77; p = 0.009). Multiple micronutrient (≥3) deficiencies also predicted poor EFS (HR = 1.69; p = 0.001) and OS (HR = 1.83; p < 0.001) in the whole cohort. CONCLUSIONS: Selenium deficiency was independently predictive of adverse outcomes in childhood cancer, particularly in haematological malignancies. Zinc deficiency adversely affected solid tumours. The adjunct use of micronutrient supplementation in paediatric malignancies should be explored.


Asunto(s)
Neoplasias Hematológicas , Desnutrición , Neoplasias , Selenio , Niño , Cobre , Ácido Fólico , Humanos , Estudios Longitudinales , Desnutrición/epidemiología , Micronutrientes , Neoplasias/epidemiología , Prevalencia , Estudios Prospectivos , Vitamina B 12 , Vitaminas , Zinc
4.
J Clin Oncol ; 38(32): 3785-3793, 2020 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-32931400

RESUMEN

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a significant toxicity of chemotherapy. Olanzapine is recommended in adult patients for the prevention of CINV but has not been prospectively investigated in children. METHODS: This investigator-initiated, randomized, open-label trial evaluated olanzapine in children (ages 5-18 years) scheduled to receive the first cycle of highly emetogenic chemotherapy (HEC). All participants received aprepitant, ondansetron, and dexamethasone during and 2 days after chemotherapy. Participants in the study group additionally received oral olanzapine 0.14 mg/kg/day (rounded to the nearest 2.5 mg; maximum, 10 mg) during the chemotherapy block and 3 days postchemotherapy. The primary objective was to compare complete response (CR) rates (no vomiting and no rescue medication) between the groups in the acute, delayed, and overall periods. Nausea comparison and safety evaluation were secondary and additional objectives, respectively. The collection of outcomes and adverse events was performed daily until the completion of the overall period. RESULTS: A total of 240 patients underwent randomization. We performed a modified intention-to-treat analysis on 231 patients (116 in the control group and 115 in the study group). A higher proportion of patients in the olanzapine group achieved CR in the acute period (78% v 59%; P = .001), delayed period (74% v 47%; P < .001) and overall period (64% v 38%; P < .001) than in the control group. The proportion of patients with no nausea was significantly higher in the olanzapine group in the acute period (74% v 52%; P < .001), delayed period (74% v 47%; P < .001), and overall period (64% v 37%; P < .001). Grade 1/2 somnolence was greater in the olanzapine group (35% v 11%; P < .001). There was no grade 3/4 somnolence reported. CONCLUSION: Olanzapine significantly improved CR rates for vomiting in children receiving the first cycle of HEC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Náusea/prevención & control , Olanzapina/uso terapéutico , Vómitos/prevención & control , Adolescente , Antieméticos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Dexametasona/uso terapéutico , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Vómitos/inducido químicamente
5.
Am J Blood Res ; 10(4): 90-96, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32923088

RESUMEN

BACKGROUND: Regulatory T cells (Tregs) modulate immune system by suppressing other immune cells. In current exploratory era of immunotherapy, the detailed enumeration data of Tregs cells in pediatric AML is lacking. AIM: Serial assessment of Treg absolute values in pediatric AML at diagnosis and follow-up; and correlating with outcome. STUDY DESIGN: Prospective study. METHODS: Study objectives were determining Tregs (CD4+CD25+Foxp3+) were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse in 30 consecutive pediatric AML patients. RESULTS: Patients with AML had higher baseline Treg frequencies than controls (P=0.0001). Female patients, WBC > 50,000 × 103/L and hypoalbuminemia were significantly associated with high Treg absolute values. Baseline Tregs were not associated with DFS, EFS and OS. Tregs significantly decreased after induction chemotherapy (P=0.028). Using generalized-estimating-equation regression model, Treg absolute numbers continued to decrease at each assessment time point from post-induction till 6 months follow-up (P=0.029) in those who are in continuous CR; however, in those patients who relapsed, Tregs did not change from post-induction till last follow-up preceding relapse (P=0.39). CONCLUSIONS: This first study in pediatric AML demonstrates that Tregs are increased at diagnosis; the increased number is significantly associated with female gender and high WBC count. Tregs decrease after induction chemotherapy as compared to their baseline value. Post CR, Treg absolute values continue to decrease significantly in those who stay in CR but not so in those who relapse; this suggests their possible role in leukemogenesis.

6.
Indian Pediatr ; 57(6): 508-511, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-32221052

RESUMEN

OBJECTIVE: We compared Vascular Endothelial Growth factor (VEGF) and Thrombospondin-1 between patients with progressive paediatric malignancies randomized to metronomic chemotherapy versus placebo to determine their role as biomarker. METHODS: In this double-blinded, placebo-controlled randomized study of 108 progressive pediatric malignancies, serum VEGF and thrombospondin-1 levels were evaluated using ELISA at baseline, A2 (week-9 or earlier if progressed) and A3 (week-18 or earlier if progressed). RESULTS: Mean VEGF and thrombospondin-1 at baseline, A2 and A3 and the change from baseline to A2 were not different between two groups. In metronomic arm, responders (those completing 3 cycles) had significantly lower mean (SD) baseline VEGF levels [659.7(362.1) vs 1143.9 (622.0) µg/mL] (P=0.002) and significant decrease in thrombospondin-1 from baseline to A2 [-4.43(8.0) µg/mL vs 1.7(11.3) µg/mL] (P=0.04), as compared to non-responders. Similar changes were not observed in responders on placebo arm. No consistent trend of these biomarkers was observed. CONCLUSIONS: VEGF and thrombospondin-1 are not reliable biomarkers for response to metronomic chemotherapy.


Asunto(s)
Neoplasias , Trombospondina 1 , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Niño , Humanos , Neoplasias/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular
7.
J Psychosoc Oncol ; 36(5): 658-666, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30862311

RESUMEN

PURPOSE: To determine the prevalence of poor food knowledge and food restrictions among families of children with cancer and assess their impact on nutritional outcomes. METHODS: In this cross-sectional study of 700 families of children with cancer who attended a referral cancer clinic, parents were asked 9 questions about nutritional knowledge ("Knowledge score") and 12 questions about food restrictions ("Restriction score"). Secondary outcomes included the nutritional status of children and possible socio-demographic associations of poor food knowledge. FINDINGS: Commercial foods were considered more nutritious than homemade foods. Restriction of protein and energy-rich foods was frequent. Low knowledge scores were associated with rural background, poverty, and illiteracy. Low parental knowledge scores were associated with low weight and low height of the child. High restriction scores were associated with low weight but not low height. CONCLUSIONS AND IMPLICATIONS: Harmful perceptions are widely prevalent in parents of children with cancer and targeted educational interventions may have a role in improving malnutrition in these children.


Asunto(s)
Trastornos de la Nutrición del Niño/epidemiología , Familia/psicología , Conducta Alimentaria , Conocimientos, Actitudes y Práctica en Salud , Neoplasias/terapia , Fenómenos Fisiológicos de la Nutrición , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , India/epidemiología , Lactante , Masculino , Factores Socioeconómicos
8.
JAMA Oncol ; 3(9): 1222-1227, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28384657

RESUMEN

IMPORTANCE: Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. OBJECTIVES: To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. INTERVENTIONS: One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. MAIN OUTCOMES AND MEASURES: The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. RESULTS: A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy. CONCLUSIONS AND RELEVANCE: Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01858571.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias/tratamiento farmacológico , Administración Metronómica , Administración Oral , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Celecoxib/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Método Doble Ciego , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Elementos de Respuesta , Retratamiento , Sarcoma de Ewing/tratamiento farmacológico , Tasa de Supervivencia , Talidomida/administración & dosificación , Factores de Tiempo
9.
Pediatr Hematol Oncol ; 34(1): 29-35, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28287332

RESUMEN

Increased obesity in leukemia survivors has been attributed to chemotherapy and radiation. Data on total energy intake (TEI) and total energy expenditure (TEE) are lacking in obese childhood leukemia patients after completion of therapy from India. We conducted a cross-sectional study in pediatric acute leukemia patients after completion of therapy wherein energy intake was assessed by 24-hour recall method. TEE was calculated using Harris-Benedict equation, by assessing the physical activity level using Physical Activity Questionnaire for children and basal metabolic rate by World Health Organization equation. Indian Academy of Pediatrics 2015 guidelines for BMI were used for defining overweight and obesity. Nutritional status was assessed in 150 leukemia patients after completion of therapy. Twenty-five percent of leukemia patients after completion of therapy were overweight and obese versus 11% of healthy controls (p = 0.042). The mean ratio of TEI/required energy intake (REI), TEE/required energy expenditure (REE), and (TEI:REI)/(TEE:REE) were significantly higher in overweight and obese group versus nonobese survivors (p < 0.001, p = 0.091, p < 0.001, respectively). Multivariate analysis showed higher income (HR-2.3, p = 0.04), increased TEI/REI (HR-4, p = 0.049) and higher (TEI:REI)/(TEE:REE) (HR-3.1, p = 0.039) to be significant factors predicting obesity. Obesity in leukemia patients after completion of therapy is associated with increased energy intake, causing imbalance between energy intake and TEE in these patients.


Asunto(s)
Ingestión de Energía , Metabolismo Energético , Leucemia/terapia , Obesidad , Encuestas y Cuestionarios , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Obesidad/etiología , Obesidad/fisiopatología , Obesidad/terapia
10.
J Nucl Med ; 58(4): 577-583, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27754902

RESUMEN

Data about the significance of 18F-FDG PET at interim assessment and end of treatment in pediatric Hodgkin lymphoma (HL) are limited. Methods: Patients (≤18 y) with HL were prospectively evaluated with contrast-enhanced CT (CECT) and PET combined with low-dose CT (PET/CT) at baseline, after 2 cycles of chemotherapy, and after completion of treatment. Revised International Working Group (RIW) criteria and Deauville 5 point-scale for response assessment by PET/CT were used. All patients received doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine chemotherapy along with involved-field radiotherapy (25 Gy) for early stage (IA, IB, and IIA) and advanced stage (IIB-IV) with bulky disease. Results: Of the 57 enrolled patients, median follow-up was 81.6 mo (range, 11-97.5 mo). Treatment decisions were based on CECT. At baseline, PET/CT versus CECT identified 67 more disease sites; 23 patients (40.3%) were upstaged and of them in 9 patients (39%) upstaging would have affected treatment decision; notably none of these patients relapsed. The specificity of interim PET/CT based on RIW criteria (61.5%) and Deauville criteria (91.4%) for predicting relapse was higher than CECT (40.3%) (P = 0.03 and P < 0.0001, respectively). Event-free survival based on interim PET/CT (RIW) response was 93.3 ± 4.1 versus 89.6 ± 3.8 (positive vs. negative scan, respectively; P = 0.44). The specificity of posttreatment PET/CT (Deauville) was 95.7% versus 76.4% by CECT (P = 0.006). Posttreatment PET/CT (Deauville) showed significantly inferior overall survival in patients with positive scan versus negative scan results (66.4 ± 22.5 vs. 94.5 ± 2.0, P = 0.029). Conclusion: Interim PET/CT has better specificity, and use of Deauville criteria further improves it. Escalation of therapy based on interim PET in pediatric HL needs further conclusive evidence to justify its use. Posttreatment PET/CT (Deauville) predicts overall survival and has better specificity in comparison to conventional imaging.


Asunto(s)
Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Adolescente , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
11.
Pediatr Blood Cancer ; 63(7): 1287-9, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27038275

RESUMEN

Health-related quality of life (HRQOL) in retinoblastoma survivors was assessed using parent proxy report of PedsQL(TM) 4.0 generic core scale. One hundred twenty-two parents of retinoblastoma survivors filled the questionnaire satisfactorily. This was compared with parent-reported HRQOL of 50 siblings. The median age of survivors was 98 (range, 60-247) months and male:female ratio was 2:1. The overall parent-reported HRQOL was significantly worse in survivors as compared to controls (74.4 ± 8.5 vs. 85.1 ± 4.6, P < 0.001). All health domains were significantly affected when compared with controls. None of the baseline and treatment-related factors predicted HRQOL.


Asunto(s)
Padres , Calidad de Vida , Retinoblastoma , Encuestas y Cuestionarios , Sobrevivientes , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Masculino , Factores Sexuales
12.
Pediatr Blood Cancer ; 63(2): 313-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26488435

RESUMEN

BACKGROUND: With current modalities, cure rates of retinoblastoma are high and hence the number of survivors is increasing. However, data on quality of life (QOL) are minimal. PROCEDURE: We analyzed QOL in 122 retinoblastoma survivors using the PedsQL(TM) 4.0 generic core scale. The self-reported questionnaire was filled by children of more than 5 years of age who had completed treatment for more than 12 months. The questionnaire consists of 23 questions on physical, social, emotional, and school domains on a scale from 0 to 4. This was converted to a scale from 0 to 100, where higher values represented better QOL. The QOL was compared with 50 siblings. Factors predicting the QOL were assessed. RESULTS: The median age of retinoblastoma survivors was 98 months (range 60-247) and 68% were males. Overall QOL was significantly poorer in retinoblastoma survivors as compared with the controls. The emotional health domain of QOL was significantly affected. Difficulties in maintaining friendships and competing were reported in the social health domain. The school health domain showed significantly higher absenteeism. However, the physical health domain, including household work, exercise, and self-care, was similar in both the groups. Lower age at diagnosis (≤ 18 months) predicted better QOL (P = 0.05), whereas age at assessment, sex, IRSS stage, and previous surgery and radiotherapy were not predictive of poor QOL. CONCLUSIONS: We found a significantly poorer QOL in retinoblastoma survivors with the psychosocial health domain being more affected than the physical domain. Age less than 18 months at diagnosis predicted better QOL.


Asunto(s)
Calidad de Vida , Neoplasias de la Retina/psicología , Retinoblastoma/psicología , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , India , Masculino , Neoplasias de la Retina/complicaciones , Retinoblastoma/complicaciones , Encuestas y Cuestionarios , Sobrevivientes , Adulto Joven
13.
Pediatr Hematol Oncol ; 32(8): 576-84, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26558505

RESUMEN

Facilities for measuring methotrexate (MTX) levels are not available everywhere, potentially limiting administration of high-dose methotrexate (HDMTX). We hypothesized that serum creatinine alteration after HDMTX administration predicts MTX clearance. Overall, 122 cycles in 50 patients of non-Hodgkin lymphoma or acute lymphoblastic leukemia aged ≤18 years receiving HDMTX were enrolled prospectively. Plasma MTX levels were measured at 12, 24, 36, 48, 60, and 72 hours; serum creatinine was measured at baseline, 24, 48, and 72 hours. Correlation of plasma MTX levels with creatinine levels and changes in creatinine from baseline (Δ creatinine) were evaluated. Plasma MTX levels at 72 hours showed positive correlation with serum creatinine at 48 hours (P = .011) and 72 hours (P = .013) as also Δ creatinine at 48 hours (P = .042) and 72 hours (P = .045). However, cut-off value of either creatinine or Δ creatinine could not be established to reliably predict delayed MTX clearance. Greater than 50% Δ creatinine at 48 and 72 hours significantly predicted grade 3/4 leucopenia (P = .036 and P = .001, respectively) and thrombocytopenia (P = .012 and P = .009, respectively) but not mucositis (P = .827 and P = .910, respectively). Delayed MTX elimination did not predict any grade 3/4 toxicity. In spite of demonstration of significant correlation between serum creatinine and Δ creatinine with plasma MTX levels at 72 hours, cut-off value of either variable to predict MTX delay could not be established. Thus, either of these cannot be used as a surrogate for plasma MTX estimation. Interestingly, Δ creatinine effectively predicted hematological toxicities, which were not predicted by delayed MTX clearance.


Asunto(s)
Creatinina/sangre , Linfoma no Hodgkin , Metotrexato/administración & dosificación , Metotrexato/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Niño , Preescolar , Femenino , Humanos , Linfoma no Hodgkin/sangre , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangre , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico
14.
Support Care Cancer ; 23(11): 3229-37, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25851802

RESUMEN

BACKGROUND: Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. RESULTS: Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. CONCLUSIONS: This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.


Asunto(s)
Antieméticos/uso terapéutico , Dexametasona/efectos adversos , Morfolinas/uso terapéutico , Náusea/prevención & control , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Ondansetrón/efectos adversos , Antagonistas del Receptor de Serotonina 5-HT3/uso terapéutico , Vómitos/prevención & control , Administración Intravenosa , Adolescente , Antiinflamatorios/uso terapéutico , Aprepitant , Niño , Preescolar , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Método Doble Ciego , Femenino , Humanos , Quimioterapia de Inducción , Masculino , Náusea/inducido químicamente , Neoplasias/tratamiento farmacológico , Ondansetrón/administración & dosificación , Ondansetrón/uso terapéutico , Ontario , Inducción de Remisión , Vómitos/inducido químicamente
15.
J Pediatr Hematol Oncol ; 34(4): e164-9, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22430589

RESUMEN

Spinal primitive neuroectodermal tumor (PNET) is rare. We present clinical, radiologic profile and treatment outcome of 15 spinal PNET patients from June 2003 to March 2010 treated with chemoradiotherapy. Median duration of backache was 6.5 months; all had features of myelopathy and/or radiculopathy; 5/15 (33.3%) patients were diagnosed initially as spinal tuberculosis. The event-free survival (EFS) was 24.73% at a median follow-up of 22 months. Complete functional recovery to treatment significantly predicted better EFS; 4 patients discontinued treatment because of poor functional recovery. It is important to recognize spinal PNET early to prevent permanent neurological damage, which in turn would improve compliance, quality of life, and perhaps EFS.


Asunto(s)
Tumores Neuroectodérmicos Primitivos/mortalidad , Neoplasias de la Columna Vertebral/mortalidad , Adolescente , Adulto , Dolor de Espalda/diagnóstico , Dolor de Espalda/mortalidad , Dolor de Espalda/terapia , Niño , Preescolar , Diagnóstico Diferencial , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/terapia , Radiculopatía/diagnóstico , Radiculopatía/mortalidad , Radiculopatía/terapia , Estudios Retrospectivos , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/mortalidad , Enfermedades de la Médula Espinal/terapia , Neoplasias de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/terapia , Tasa de Supervivencia , Tuberculosis de la Columna Vertebral
16.
Radiology ; 262(3): 956-68, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22357895

RESUMEN

PURPOSE: To prospectively examine the roles of positron emission tomography (PET)/computed tomography (CT) and conventional contrast material-enhanced CT at baseline, after two cycles of chemotherapy, and after completion of chemotherapy in pediatric patients with nonlymphoblastic non-Hodgkin lymphoma (NHL) who were treated with similar standard treatment protocols. MATERIALS AND METHODS: The institutional ethics committee approved the study protocol, and all patients were enrolled after written informed consent was obtained. Patients with nonlymphoblastic NHL were prospectively enrolled between January 2008 and March 2010. Patients underwent contrast-enhanced CT and PET/CT for staging and for response assessment after two cycles of chemotherapy (interim) and treatment completion. Complete metabolic response versus no metabolic response at PET/CT and complete response versus no complete response at contrast-enhanced CT was analyzed by using Kaplan-Meier survival analysis. RESULTS: The final study included 34 patients with nonlymphoblastic NHL (median age, 10.5 years). Baseline PET/CT and contrast-enhanced CT showed concordance in depiction of 112 disease sites; PET/CT depicted 18 more disease sites and two fewer disease sites than contrast-enhanced CT (P = .0003). Disease in five of 34 patients was upstaged, and disease in no patient was downstaged at PET/CT. There was 100% (four of four) concordance between bone marrow involvement at biopsy and stage at PET/CT. The median length of follow-up was 20.3 months. Response at interim PET/CT and contrast-enhanced CT could not predict progression-free survival (PFS) (P = .083 and .18, respectively) or overall survival (OS) (P = .159 and.08, respectively). Posttreatment PET/CT and contrast-enhanced CT findings could predict PFS (P = .036 and .002, respectively) and posttreatment contrast-enhanced CT findings could predict OS (P = .035); however, posttreatment PET/CT findings could not predict OS (P = .067). CONCLUSION: PET/CT depicts additional sites compared with contrast-enhanced CT and results in upstaging of disease. Either PET/CT or contrast-enhanced CT may be used for response assessment and prognostication in stage III or IV nonlymphoblastic pediatric NHL.


Asunto(s)
Linfoma no Hodgkin/diagnóstico por imagen , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X/métodos , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Medios de Contraste , Diatrizoato , Femenino , Fluorodesoxiglucosa F18 , Humanos , Yopamidol/análogos & derivados , Estimación de Kaplan-Meier , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/patología , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Interpretación de Imagen Radiográfica Asistida por Computador , Radiofármacos , Sensibilidad y Especificidad , Resultado del Tratamiento
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