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PubMedDate not supplied

Pharmacokinetic analysis of gentamicin thrice and single daily dosage in pediatric cancer patients.

Fifty-two children suffering from different types of malignancies were included and evaluated for the pharmacokinetics of gentamicin thrice or single daily dosage protocols. All the study population received a total dose of 5 mg/kg daily. Thirty children received gentamicin thrice daily, and 22 were treated using the single daily protocol; all had fever and neutropenia when included. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood gentamicin samples. The mean (SD) t 1/2 (h), clearance (mL/min/BSA), Vss (L/kg), Cmax (micrograms/mL), and Cmin (micrograms/mL) were 3.05 (1.0) and 3.9 (0.6) h, 136 (61.3) and 99.9 (65.3) mL/min/BSA, 0.4035 (0.167) and 0.457 (0.17) L/kg, 5.2 (2.0) and 11.5 (4.2) micrograms/mL, 0.8 (0.6) and 0.18 (0.1) microgram/mL for thrice and single daily dosage schedules, respectively. The single gentamicin daily dose protocol had a significantly longer t 1/2, shorter clearance normalized to BSA, higher Cmax, and lower Cmin in comparison with the thrice daily schedule. We recommend the use of gentamicin at 5 mg/kg daily delivered as a single daily dose for pediatric cancer patients with fever and neutropenia, in spite of the measured pharmacokinetic differences, which in our opinion have no clinical significance.

Adolescent↗

PubMed2002

Interventions for anemia in pediatric cancer patients.

BACKGROUND: Children with cancer frequently develop anemia both from the disease and from chemo- and radiotherapy. Considered a manageable complication, anemia is often not treated until it becomes severe, i.e., hemoglobin (Hb) level <or= 7 g/dL. The most frequent treatment employed for anemia in children with cancer is blood transfusion. PROCEDURE AND RESULTS: A retrospective survey of 74 children demonstrated that the use of blood transfusions increased as the intensity of therapy increased. At least one blood transfusion was administered to 12.5% of children who received standard chemotherapy, and to 59.5% of children who received intensive chemotherapy. These data also show that a substantial percentage of children did not receive treatment for intensive or high-dose chemotherapy, whereas anemia occurred in almost all patients. Recombinant human erythropoietin (rHuEPO, epoetin alfa) has been shown to be effective in adults in increasing Hb levels and in improving outcomes, including quality of life and survival. The use of epoetin alfa in children has not been extensively studied, and only a few clinical trials have been conducted. CONCLUSIONS: The good results seen in adults, data thus far in pediatrics, and the need for alternatives to transfusions in children make epoetin alfa an attractive treatment option for anemia in pediatric cancer patients. Clinical studies are underway to evaluate the efficacy and safety of epoetin alfa in increasing Hb values and improving outcomes in children with cancer.

Anemia↗

PubMed2006

Importance of clinical and epidemiological research in defining the long-term clinical care of pediatric cancer survivors.

With the increasing number of long-term survivors of childhood cancer, there continues to be a critical need for development and implementation of evidence-based recommendations for clinical follow-up. In order to establish and maintain health-related follow-up guidelines, it is important to recognize the attributes of research from which the recommendations may be formulated. Issues including study design and clinical research methodology, completeness of long-term follow-up for the applicable study population, approaches for assessment of treatment-related exposures, methods utilized for ascertainment and characterization of outcomes, and recognition of potential modifiers of risk (e.g., demographic or treatment-specific factors) are all important considerations when evaluating the results of available research. For the future, greater attention will not only need to be given to further development and maintenance of recommendations for follow-up, but to the scientific evaluation of the recommendations to determine the subsequent impact on health status and quality of life among pediatric cancer survivors.

Adolescent↗

PubMed2007

Ovarian repositioning in pediatric cancer patients: Flexible techniques accommodate pelvic radiation fields.

Treatments for childhood cancer and consequent long-term survival rates continue to improve. As the success of these therapies advances, premature ovarian failure and sterility have become an increasingly evident long-term morbidity. Abdominal and pelvic radiation have been specifically shown to induce early menopause and decreased fertility. In order to minimize radiation injury, we utilized novel techniques to reposition ovaries in two girls with pelvic tumors prior to initiation of pelvic radiation. One girl with a sacral Ewing sarcoma underwent laparoscopic anterior suspension of the ovaries, using a simple and easily reversible technique. The second patient, who underwent hysterectomy for a recurrent uterine rhabdomyosarcoma, underwent widely lateral and cephalad repositioning of the ovaries. Both procedures were well tolerated, with no significant morbidity. In both cases the ovaries were moved well beyond the planned radiation field. We propose that open or laparoscopic ovarian repositioning in children is a simple, flexible, and reversible option to reduce radiation injury to the ovaries in pediatric cancer patients.

Child↗

PubMed1984

Secondary thyroid neoplasms in pediatric cancer patients: increased risk with improved survival.

Between 1973 and 1983, eight children who had undergone successful multimodal management of malignant tumors developed secondary thyroid neoplasms. The primary tumors were acute lymphocytic leukemia in three, Wilms' tumor in two, and Hodgkin's disease, rhabdomyosarcoma, and ganglioneuroblastoma in one each. During this period, 174 long-term survivors with these five diagnoses were enrolled in our tumor registry, yielding a 4.6% incidence of secondary thyroid neoplasms. All eight patients received both radiation and chemotherapy. The mean radiation dose was 2,700 r with a calculated thyroid dose of 2,140 r (range, 5 to 4,200 r). Age of diagnosis of the primary tumors ranged from 1 to 8 2/12 years (mean, 5 years), and the latent period between treatment and development of the thyroid lesions averaged 6 1/2 years. Thyroid neoplasms presented at an average age of 11 4/12 years. Five patients developed solitary adenomas, one presented with multiple adenomas, and two had follicular carcinoma with regional lymph node metastases. Although thyroid neoplasms are rare in childhood, clinically apparent thyroid tumors have been observed in up to 2.5% of children following radiation exposure (mean follow-up, 24 years). The reported latent period before the development of thyroid neoplasms in irradiated patients is at least 10 years, with the peak incidence occurring 20 to 25 years after exposure. This study documents a 4.6% incidence of subsequent thyroid neoplasms in pediatric cancer patients within a relatively short follow-up period (mean, 11 years). These thyroid tumors occurred at an earlier age (mean, 11.5 years) and with a shorter latent period (mean, 6.5 years) than would be predicted from previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1998

[Recombinant human erythropoietin in anemia associated with pediatric cancer: study of the identification of predictors of response].

OBJECTIVE: Cancer is frequently associated with anemia and may be related to inadequate erythropoietin production. The objective of this study was to assess the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in increasing hemoglobin levels and reducing the need of blood transfusions in children with cancer, as well as to identify predictors of the response to r-HuEPO. PATIENTS AND METHODS: A pilot trial was performed including 25 patients with solid malignant tumors receiving cyclic chemotherapy, r-HuEPO was administered subcutaneously, 150 U/kg/day 5 times a week for 12 consecutive weeks. Response was defined as the achievement of a Hb increase of at least 2 g/dl without blood transfusions. Patients were compared to history matched controls. RESULTS: Baseline parameters were similar (p > 0.05) in both groups. The mean Hb increase was greater in the r-HuEPO group compared to controls (2.6 vs 0.1 g/dl; p < 0.001) and the mean units of blood transfused were lower in treated patients (0.32 vs 2.36; p < 0.05). Response to r-HuEPO was achieved in 19 (76%) patients. Low baseline erythropoietin levels and an increase in Hb of at least 0.5 g/dl after 3-4 weeks of treatment defined a greater probability of response. No serious adverse effects were observed. CONCLUSIONS: r-HuEPO treatment represents a safe and effective means of increasing Hb levels and reducing blood requirements in pediatric cancer patients receiving chemotherapy and the prediction of response may be based on baseline serum erythropoietin levels and on the variation of Hb levels after 3-4 weeks of treatment.

Adolescent↗

PubMedDate not supplied

Safety, tolerability, antiemetic efficacy, and pharmacokinetics of oral dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

PURPOSE: The safety, antiemetic efficacy, and pharmacokinetics of single oral doses of dolasetron, a new highly selective 5-HT3 receptor antagonist, were evaluated in children with cancer undergoing treatment with moderately to highly emetogenic chemotherapy. PATIENTS AND METHODS: A total of 32 children, ages 3 to 18 years, were enrolled in a nonrandomized, multicenter, open-label, dose-escalation study. Three oral dose levels (0.6, 1.2, or 1.8 mg/kg) were studied. Safety, efficacy, and pharmacokinetic parameters were assessed over 24 hours at each dosage level. RESULTS: The most effective dose was 1.8 mg/kg; 60% of the patients achieved a complete or major response (< or =2 emetic episodes in 24 hours). A complete response was achieved in 3 of 9 patients (33%) who received 0.6 mg/kg, 4 of 13 (31%) patients who received 1.2 mg/kg, and 5 of 10 (50%) patients who received 1.8 mg/kg of dolasetron. Overall, dolasetron was well tolerated. Adverse events were mild and similar to those reported in adults. Peak plasma concentrations (Cmax) of dolasetron's active reduced metabolite, MDL 74,156, were dose proportional and occurred, on the average, within 1 hour of oral administration. The half-life (t1/2) in plasma was approximately 6 hours for all dose levels, and the mean clearance (CLapp) was unrelated to dose. CONCLUSIONS: Oral dolasetron is safe and effective in reducing chemotherapy-induced nausea and vomiting, particularly at the 1.8-mg/kg dose level. These results support further evaluation of oral dolasetron in larger randomized clinical trials in the pediatric cancer population.

Administration, Oral↗

PubMed2026

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗

PubMed2006

Pediatric cancers are infiltrated predominantly by macrophages and contain a paucity of dendritic cells: a major nosologic difference with adult tumors.

PURPOSE: Adult cancer is frequently preceded by a period of prolonged chronic inflammation caused by infectious microbial agents or physical or chemical irritants. By contrast, an association between the classic pediatric neoplasias and inflammatory triggers is only rarely recognized. We hypothesized that the difference could be reflected in the inflammatory cell infiltrates of pediatric and adult cancer. EXPERIMENTAL DESIGN: Three investigators retrospectively studied 27 pediatric and 13 adult cancers at first diagnosis by immunohistochemistry. Inflammatory cells were identified and counted, and their location in relation to tumor tissue was analyzed. RESULTS: A majority of tumor-associated leukocytes (TAL) in adult tumors were located at the edges of tumor islands forming inflammatory foci between the supporting stroma and the malignant infiltrate. In contrast, TALs in pediatric tumors were scattered within the malignant tumor islands. In adult tumors, TALs were composed of diverse leukocyte types; but in pediatric tumors, the infiltrating cells were predominantly macrophages that accumulated in areas of necrosis within the tumors. The most striking feature in the pediatric tumors was the virtual absence of dendritic cells. The proportion of intratumoral dendritic cells in pediatric samples was 4.1%; whereas in adult tumors, they formed 36.9% of TALs within the tumor islands and 25.1% around the tumors. CONCLUSIONS: We conclude that TALs in pediatric cancers are composed mainly of macrophages and largely devoid of dendritic cell. The findings may provide a major nosologic difference reclassifying pediatric and adult tumors based on nominal inflammatory and noninflammatory etiologies.

Adolescent↗

PubMedDate not supplied

Smoking interventions delivered by pediatric dentists: special recommendations for pediatric cancer patients.

Child and adolescent cancer patients who use tobacco present challenging management problems for the pediatric dentist. An approach to counseling patients about their oral health risks secondary to their cancer treatment, which can be adversely impacted by tobacco use, is discussed. Strategies for conducting dental examinations with pediatric cancer patients with attention to potential tobacco-related complications are also provided.

Adolescent↗

PubMed1997

The U.S. pediatric cancer clinical trials programmes: international implications and the way forward.

The four national paediatric cancer clinical trials organisations in the United States--the Children's Cancer Group, the National Wilms' Tumor Study Group, the Intergroup Rhabdomyosarcoma Study Group and the Pediatric Oncology Group--were formed in 1955, 1969, 1972 and 1979, respectively. Together, the Children's Cancer Group and Pediatric Oncology Group serve as a national registry of nearly all childhood cancers in the United States, provide a national network of communication for researchers, care providers and families of paediatric patients with malignant disease and conduct laboratory investigations and clinical trials of new treatments of cancers in infants, children, adolescents and young adults. Nearly 95% of patients with cancer in the United States who are below 15 years of age are registered by the Children's Cancer Group and the Pediatric Oncology Group and more than half of American children with cancer are entered into at least one trial by a paediatric group. Improved survival of children receiving treatment according to well-defined protocols in specialised children's centres, in contrast to children who received treatment outside of these centres, has been shown for those with acute lymphoblastic leukaemia, lymphoma, Wilms' tumour, medulloblastoma, rhabdomyosarcoma and Ewing's sarcoma. By the year 2000, the overall cure rate for United States children and adolescents with cancer should exceed 85%. To reach this goal, the way forward will depend on international collaboration, implementation of global harmonisation, prevention of the erosion of biomedical research and clinical trials by the managed health care industry, increased public and private financial support and continued recruitment into paediatric oncology of brilliant and dedicated young investigators. The specific challenges ahead include: (1) transferring the knowledge, methodologies and technologies to countries that are less fortunate; (2) conducting multinational clinical trials in conjunction with paediatric cooperative groups in other countries; (3) accessing older adolescent patients who currently do not participate in cooperative group trials; (4) merging clinical trials by adult collaborative groups that overlap with the paediatric groups, as in acute lymphoblastic leukaemia, acute myelogenous leukaemia, Hodgkin's disease, osteosarcoma and germ cell tumours; (5) establishing a stable source of funding for national and international cooperative paediatric cancer clinical trials; (6) creating an informatics system that can link paediatric cooperative group operation centres around the world, and the institutions within each collaborative group; and (7) securing the support of the insurance industry and government in covering clinical trials.

Adolescent↗

PubMed2006

Pediatric cancer survivorship: research and clinical care.

Regardless of how one defines survivorship, more than 10 million individuals in the United States have been treated for a malignant disease; about 250,000 were younger than 21 years of age at diagnosis. Thirty years ago, pediatric oncologists recognized that children with cancer might be cured by adding chemotherapy to surgery and radiation. Studies were then begun of complications that could reduce survival or the quality of survival, and that might be associated with previous therapy. The complications were termed late effects, and studies focused on patients who were likely to be cured, or less likely to succumb to the original cancer than they were to experience disabilities. Clinical trials tested whether changes in therapy to reduce complications could maintain the same excellent survival rates. During the last 20 years, articles detailing late effects and the relationship between therapy and outcome have been published. This article reviews the progress made in understanding the outcomes reported and the efforts made to improve the quality of long-term survival for children and adolescents. Several questions remain regarding the long-term complications of therapy. Clinicians need more data regarding the effects of aging to guide them in managing former patients. Caregivers and pediatric cancer survivors who are now adults seek the optimal venue in which to receive care as independent adults. In addition, medical oncologists need to determine whether the models for research and clinical care of survivors created in pediatric oncology can be applied to survivors of adult-onset cancer.

Adolescent↗

PubMed2005

ERBB2 in pediatric cancer: innocent until proven guilty.

Adult oncologists and their research colleagues have "led the charge" in the war on cancer. Their efforts have generated effective new chemotherapies that target cancer causing molecular alterations. It is hoped that these successes will be repeated within the pediatric oncology community. Testing whether molecular targeted therapies of adult cancers are also effective against childhood cancers might allow the rapid introduction of these exciting new agents into the pediatric clinic. However, it is imperative that we do not introduce blindly these agents into the pediatric population. We must ensure that molecular targets in adult cancers also fulfill a number of important criteria within the pediatric disease. This review addresses the issues surrounding the identification of molecular targets in pediatric cancers by focusing on studies of the ERBB2 oncogene.

Biomarkers, Tumor↗

PubMed2005

Clinical and microbiologic determinants of serious bloodstream infections in Egyptian pediatric cancer patients: a one-year study.

OBJECTIVES: Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored policies for the treatment of patients with febrile neutropenia following chemotherapy can then be created. PATIENTS AND METHODS: Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed bloodstream infection were studied retrospectively. RESULTS: A total of 328 BSI occurred in 1135 febrile episodes in pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%) and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in 45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and fungal infection, lower respiratory tract infections and persistent neutropenia at day seven. CONCLUSIONS: In a large population of children, common clinical and laboratory risk factors were identified that can help predict more serious BSI. These results encourage the possibility of a more selective management strategy for these children.

Adolescent↗

PubMed2005

[Infectious complications in pediatric cancer patients].

Infectious complications are still a major cause of morbidity and mortality in pediatric patients undergoing therapy for malignancy. Therapy-induced neutropenia is the most important risk factor for infectious risk in pediatric patients with cancer, but other factors, such as alterations in skin/mucosal barriers, and defects in cell-mediated or humoral immunity also contribute to the risk for infection. In most centers, about two thirds of bacteremic isolates are gram-positive pathogens, whereas gram-negative organisms are isolated less frequently, but are associated with considerably higher mortality rates. Prolonged neutropenia increases the risk for invasive fungal infection. In most cases, fever is an important and early indication of serious infection, particularly in children with neutropenia. Discrimination between serious and inconsequential infection in febrile children with neutropenia at the time of presentation is difficult, and serum markers have not been proven to reliably indicate infection. Although several groups investigate risk categories based on clinical tests or the genetic background, the current paradigm is to treat all pediatric patients with neutropenia and fever with intravenous broad-spectrum antibiotics. It is hoped that the identification of one or more predictive factors may be useful for tailoring antibiotic prophylaxis and therapy in children with cancer.

Adolescent↗

PubMed1985

Anticipatory nausea and vomiting in pediatric cancer patients.

The purpose of this study was to determine the prevalence and correlates of anticipatory nausea and vomiting in a sample of pediatric patients with cancer who were receiving outpatient chemotherapy. Forty male and female patients representing a broad range of diagnoses were interviewed with their parents concerning nausea and vomiting before and after chemotherapy. Anticipatory nausea was reported by 28.8% of the sample; anticipatory vomiting was present in 20% of the sample. An additional 9% had experienced anticipatory nausea and vomiting in the past but not currently. Anticipatory nausea and vomiting was positively correlated with the emetic potential of chemotherapeutic regimens and the severity of nausea and vomiting after chemotherapy; anticipatory nausea and vomiting most often developed within the first 4 months of treatment. Onset of anticipatory nausea and vomiting usually occurred two to four hours before treatment and was most severe at the actual time of drug administration. Considerable interpatient variability was observed, with treatment-related factors accounting for only 22% of the variance in the occurrence of anticipatory nausea and vomiting. These findings are considered within a behavioral framework for understanding conditioned aversions in pediatric patients with cancer. Implications for patient education, future research on the prediction of children at risk, and intervention are discussed.

Adolescent↗

PubMed1994

Pediatric cancer pain management: a survey of nurses' knowledge.

This study assesses the knowledge base of pediatric nurses in Iowa regarding cancer pain. The Iowa Cancer Pain Relief Initiative surveyed 10,000 nurses in the state of Iowa (representing approximately 25% of all actively licensed nurses in the state). A demographic question allowed pediatric nurses' responses to be separated and analyzed independently. One hundred six of the respondents indicated their primary area of practice to be pediatrics, and it is this group of respondents that was analyzed. Content analysis of questionnaires from pediatric respondents indicated that pediatric nurses cared for cancer patients regularly but had poor understanding of general principles of pain management for the cancer patient. Nurses had exaggerated concerns regarding the risk of addiction and respiratory depression associated with narcotic analgesics. They also had poor understanding of basic pharmacokinetic principles of common analgesic agents.

Adult↗

PubMed1976

Janeway Lecture: Pediatric cancer treatment: a model for oncology.

Advances in pediatric oncology are reviewed using Wilms's tumor as a model. From the period when Wilms's tumor was treated by surgery alone to the time when adjuvant radiation and chemotherapy enabled attainment of an 80% survival rate, true collaboration among surgeons, radiation therapists, and pediatricians has been the key to success. The National Wilms's Tumor Study seeks to further refine treatment so that survival rates are maximized with minimum morbidity. The lessons applicable to all in cancer management are that a team approach is essential, all forms of treatment should be weighed early, treatment should be skilled and vigorous from the beginning the biology and natural history of the tumor should be considered in treatment planning, and toxicities of all forms of treatment should be respected and ways designed for their reduction.

Child↗