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PubMed2005

Evaluation of guideline for treatment of febrile neutropenia in pediatric cancer at Siriraj Hospital.

BACKGROUND: Febrile neutropenia (FN) is a common and important clinical problem in pediatric cancer. Our Institution has developed a clinical practice guideline (CPG) for treatment of FN to assist the clinicians taking care of these patients. OBJECTIVE: To evaluate characteristics of FN, sources and causative agents of infection, applicability and effectiveness of the CPG, and factors that associated with response to treatment. MATERIALS AND METHODS: The medical records of patients with FN that had completed data from September, 2003 to May, 2005 were reviewed and analysed. RESULTS: A total of 148 FN episodes in 90 patients were analysed. The predominant underlying malignancy was acute leukemia. About 50% had absolute neutrophil count (ANC) less than 100 cells/mm3 at the beginning and at reassesment on day 3 of treatment. The causes of infection with microbiological confirmation was 25%. Urinary tract infection was the predominant source of infection and gram negative bacteria was the predominant causative agent. Sixty-two percents responded to initial treatment without changing of antibiotics. Of all episodes, 91.2% were able to complete treatment according to the CPG. The mortality rate was 1.4%. ANC of less than 100 cell/mm3 on day 3 of treatment was the significant risk factor for prolonged duration of fever and unresponsiveness to low risk regimen of antibiotics. ANC of less than 100 cell/mm3 on day 3, having hematologic malignancies, and recurrent fever were associated risks for the need for antifungal agent or referral to infectious diseases specialist or death. The pretreatment ANC more than 100 cells/mm3 was a significant predictor for the responsiveness to low risk regimen without recurrent fever. CONCLUSION: Our CPG could practically be applied in FN patients and resulted in low mortality rate.

Child↗

PubMed1990

Use of a camp setting to provide medical information to siblings of pediatric cancer patients.

It has been reported that siblings of children with cancer often lack information and understanding about their brother's or sister's disease and treatment. The purpose of this paper is twofold: (1) to describe a camping program for siblings, which was designed, in part, to provide these children with age-appropriate medical information; and (2) to report the results of a study which examined how this intervention influenced siblings' knowledge and understanding of their brother's or sister's disease. Ninety siblings between the ages of 6 and 17 who completed a pre/post camp medical information questionnaire participated in this investigation. The results revealed that younger (6- to 11-year-old) siblings attending camp for at least the second time and older (12- to 17-year-old) siblings attending camp for the first time experienced significant (p less than .05) improvement in their overall knowledge and understanding of their brother's or sister's cancer. The results also revealed positive changes in the desired direction with respect to siblings' fear or their friends' fear about catching their brother's or sister's cancer. The results of this study provide a conceptual model for other pediatric cancer facilities engaged in developing intervention programs for siblings.

Adolescent↗

PubMed2003

Clinical trials in pediatric cancer: parental perspectives on informed consent.

To better understand parental perceptions of the informed consent process in pediatric oncology clinical trials, 20 parents of newly diagnosed children at two pediatric cancer centers described their perceptions in a semi-structured interview. They recalled well the diagnosis, the general treatment plan, and the statistics of survival and/or cure, but the research nature of the clinical trials, particularly randomization, was not well understood. However, despite the need to assimilate a great deal of information, time pressure to make decisions, and reportedly high levels of distress during the discussions, parents expressed general satisfaction with the informed consent discussions with their pediatric oncology providers. However, half to two thirds of parents felt there had been inadequate discussion of alternatives to the proposed treatment and of the research nature of the protocol. While further study of the informed consent process should be conducted in larger, representative samples, the findings from this pilot study suggest that a goal of future informed consent interventions should be to improve parents' understanding of the research aspects of treatment. It is critical to parents' ability to provide informed consent that they feel satisfied that they know alternatives to proposed treatment and that they understand the randomization of treatments, which is the gold standard of clinical trials in pediatric oncology.

Adolescent↗

PubMed2005

In vivo evaluation of ixabepilone (BMS247550), a novel epothilone B derivative, against pediatric cancer models.

PURPOSE: Vinca alkaloids, agents that cause depolymerization of microtubules, are highly active in treatment of many pediatric cancers. In contrast, taxanes, agents that stabilize microtubules, are far less effective against the same cancer types. The purpose of the current study was to evaluate the antitumor activity of ixabepilone, an epothilone B derivative representing a new class of microtubule-stabilizing antimitotic agent in a wide variety of pediatric solid tumor models. EXPERIMENTAL DESIGN: Ixabepilone was administered i.v. every 4 days for three doses to scid mice bearing s.c. human rhabdomyosarcoma (three lines), neuroblastoma (four), Wilms' tumors (six), osteosarcoma (four), or brain tumors (seven). Tumor diameters were measured weekly, and tumor growth or regressions were determined. Pharmacokinetic studies were done following a single administration of drug at the maximum tolerated dose (MTD) level (10 mg/kg). RESULTS: At the MTD (10 mg/kg), ixabepilone induced objective responses (all tumors in a group achieved > or = 50% volume regression) in three of three rhabdomyosarcoma lines, three of five neuroblastomas, six of seven Wilms' tumor models, two of six osteosarcoma, and four of eight brain tumor models. However, the dose-response curve was steep with only 2 of 19 tumors models regressing (> or = 50%) at 4.4 mg/kg. In comparison, paclitaxel administered at the MTD on the same schedule failed to induce objective regressions of three tumor lines that were highly sensitive to treatment with ixabepilone. Pharmacokinetics following single i.v. administration of ixabepilone at its MTD (10 mg/kg) were biexponential with C(max) of 12.5 micromol/L, elimination half-life of 19.2 hours, and total area under the curve of 5.8 micromol/L-h. The achieved drug exposure of ixabepilone at this efficacious MTD dose level in mice is similar to those achieved in patients given the recommended phase II dose of 40 mg/m2 by either 1- or 3-hour infusion every 3 weeks, a regimen that has shown significant anticancer activity in phase II clinical trials in adult patients. CONCLUSIONS: Administered at doses ranging from 66% to 100% of its MTD in mice, the epothilone B derivative ixabepilone shows broad spectrum activity against a panel of pediatric tumor xenograft models. Pharmacokinetic analysis indicates that the systemic ixabepilone exposure achieved in mice at its MTD is similar to that achieved in patients at the recommended phase II dose of 40 mg/m2 administered every 3 weeks. Importantly, the present results showed a clear distinction in sensitivity of pediatric solid tumors to this epothilone derivative compared with paclitaxel.

Animals↗

PubMedDate not supplied

Gender differences in psychological adaptation and coping in parents of pediatric cancer patients.

This study investigated differences in psychological distress and coping styles between fathers and mothers of pediatric cancer patients, over a 1-year time period. Also examined were (dis)similarities in couples in distress and coping, and the relationship between (dis)similarities in coping and psychological functioning of both members of a couple. Parents (n = 124, 62 couples) were assessed at diagnosis, at 6 and 12 months. Fathers and mothers experienced higher levels of psychiatric symptomatology and psychological distress at diagnosis than men and women of a normgroup. Distress declined significantly with time. Although parents did not report more symptoms than the normgroup 12 months post-diagnosis, they still were psychologically out of balance. Contrary to findings in the general population, no differences were found between fathers and mothers in psychiatric symptoms or psychological distress on any of the measurements. Only a few gender differences in coping were found. Fathers used more active-problem focusing at diagnosis and a less palliative reaction pattern at 12 months than did mothers. Mothers used more social-support seeking on all measurements. A tendency for similarity in the use of the coping styles within couples was found. Discrepancies in coping in couples were positively related to distress in fathers at diagnosis. However, 12 months later, the more discrepant the couples were in their coping preferences the more distress the mothers indicated.

Adaptation, Psychological↗

PubMed2006

Psychological adjustment of parents of pediatric cancer patients revisited: five years later.

We investigated the psychological functioning of parents of children suffering from pediatric cancer using a prospective design over a five-year time period. Parents of children diagnosed with cancer participated at diagnosis (T1), six months (T2), twelve months (T3), and five years later (T4, n = 115). Repeated measures ANOVAs were calculated for the three measures of psychological distress (GHQ, SCL-90 and STAI-S) to examine changes over time and gender differences. Independent T-tests were computed to examine differences between the mean scores of the parents at T4 and the norm groups. The effects of health status and earlier levels of distress on T4 functioning were examined using ANOVA and partial correlational analysis. Results showed that levels of reported distress, psychoneurotic symptoms and state anxiety significantly decreased across time to normal levels at T4 except on the GHQ. A significantly higher percentage of parents (27%) than in the norm group (15%) showed clinically elevated scores on the GHQ. Mothers had higher scores than fathers only on state anxiety. Parents of relapsed children reported higher anxiety levels than parents of surviving and deceased children. Psychological functioning at T1 was significantly related to functioning at T4. These results support the conclusion that although parental distress decreases with time, a significant number of parents still suffer from clinical distress after five years. Parents of relapsed children are at risk for long-term psychological problems as are those with higher levels of psychosomatic complaints at diagnosis.

Adaptation, Psychological↗

PubMed1997

Variables associated with anticipatory nausea and vomiting in pediatric cancer patients receiving ondansetron antiemetic therapy.

Investigated the prevalence of anticipatory nausea and vomiting (ANV) among 59 pediatric cancer patients who had routinely received ondansetron (Zofran) antiemetic therapy and determined patient- and treatment-related factors associated with ANV. Of the sample, 59% indicated at least mild ANV symptoms, suggesting that a significant number of patients report ANV and are bothered by it, despite the use of Zofran. These children were compared to those reporting no ANV symptoms. Most ANV symptomatology was consistent with a traditional classical conditioning model although cognitive processes may also play a role. Children with greater expectations of severe postchemotherapy vomiting and those who were more distressed by nausea and vomiting were more likely to experience ANV symptoms. Implications for psychological and pharmacological treatments of ANV are discussed.

Adolescent↗

PubMed1992

Immunological evaluation of pediatric cancer patients receiving recombinant interleukin-2 in a phase I trial.

Immunological evaluations were performed on 14 pediatric cancer patients who received human recombinant interleukin-2 (rIL-2) as a bolus intravenous infusion every 8 h for 5 consecutive days in a phase I trial. Three-to-four patients were treated at dose levels of 10, 30, 60, and 100 x 10(3) Cetus U/kg. Six of the patients had stage D neuroblastoma; the remainder had other solid tumors or leukemias. Infusion of rIL-2 was associated with a rapid margination of IL-2-responsive cells followed by demargination and heightened proliferative and cytotoxic activity after therapy was completed. The predominant phenotypic change in circulating peripheral blood mononuclear cells (PBMC) was an increase in CD2 expression by CD56+ natural killer (NK) cells. Appearance of CD2+ CD56+ cells in the circulation correlated with increased lymphokine-activated killer (LAK) cell activity as defined by the ability to kill NK-resistant Daudi tumor cells in vitro. Sustained LAK activity appeared to be dependent on the bioavailability of rIL-2 in vivo as well as in vitro. After rIL-2 therapy, PBMC that were highly responsive to rIL-2 (activated and "poised" LAK cells) persisted for at least 72 h. In the patients tested, increased lysis of autologous and/or allogeneic, histologically similar tumor cell lines was also observed after therapy. The immunoenhancing effects of rIL-2 occurred even at the lower doses used in this study. However, an objective tumor response was not observed in any of the patients.

Adolescent↗

PubMedDate not supplied

Pediatric cancer research from past successes through collaboration to future transdisciplinary research.

Multidisciplinary collaboration in therapeutic research in childhood cancer has been responsible for enormous improvements in outcomes. Many of the improvements have resulted from large clinical trials carried out in multisite settings through the Children's Oncology Group (COG) and its predecessors, the Children's Cancer Group, the Pediatric Oncology Group, the National Wilms' Tumor Study, and Intergroup Rhabdomyosarcoma Study Groups. Childhood acute lymphoblastic leukemia models the past success of 35 years of randomized clinical trials that resulted in survival rates of around 80%. However more can be done to improve both survival rates and the quality of survival. Areas that can benefit from a transdisciplinary model of research are discussed, as well as challenges to this form of collaboration.

Adolescent↗

PubMedDate not supplied

Security and maximal tolerated doses of fluvastatin in pediatric cancer patients.

BACKGROUND: The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. OBJECTIVE: The objective of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. METHODS: This study was carried out in a third level Social Security Hospital in Mexico City. We included pediatric patients from April 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was given p.o. at doses of 2 mg/kg/day for 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, laboratory assays and a questionnaire given to each patient. RESULTS: Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are alive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses were administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Toxicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. CONCLUSIONS: Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials.

Adolescent↗

PubMed1990

[Autologous bone marrow transplantation in pediatric cancer].

Since May 1979, 47 patients with pediatric malignancy aged 1 to 18 years (median: 7) were treated with cryopreserved autologous bone marrow transplantation (ABMT) in the department of pediatrics, National Cancer Center Hospital. The malignancies were acute non-lymphocytic leukemia (n = 8), acute lymphocytic leukemia (n = 5), osteosarcoma (n = 7), neuroblastoma (n = 6), brain tumor (n = 5), rhabdomyosarcoma (n = 4), retinoblastoma (n = 3), Ewing's sarcoma (n = 3), non-Hodgkin's lymphoma (n = 2), malignant histiocytosis (n = 1), hepatoblastoma (n = 1), malignant melanoma (n = 1) and malignant neuroepithelioma (n = 1). Conditioning regimens for solid tumors were multi-agent high-dose chemotherapy, mainly consisted of cyclophosphamide (CY) 120 mg/kg or melphalan 180mg/m2 and that for hematological malignancies were CY with fractionated total body irradiation (12 Gy). In vitro purging by 4-hydroperoxycyclophosphamide was performed in 12 leukemia patients and 5 solid tumor patients. Of the 13 patients with acute leukemia, 1 died from relapse 1 year after the unpurged marrow transplantation and 1 relapsed in the testis. Remaining 11 patients are alive in continuous complete remission with a median follow up of 30 months (range, 2 to 65 months) after transplantation. The disease-free survival rate of them was 78%. Of the 34 patients with solid tumor, 21 patients died, their cause of death were relapse in 18 and each one of infection, graft failure and brain hemorrhage. Thirteen patients are alive without disease with a median follow up of 28 months (range, 2 to 107 months) posttransplant. The longest survivor is a brain tumor girl, and there are 5 other long survivors; 2 of them are osteosarcoma and each one of rhabdomyosarcoma, Ewing's sarcoma and malignant histiocytosis. The disease-free survival rate of total 34 solid tumor patients is 29%, but that of 17 patients who received ABMT in responsive and minimum tumor residue (MTR) period was 69%. These results suggest that autologous bone marrow transplantation is an effective and tolerable treatment for poor prognostic pediatric malignancies, especially for acute leukemia and such solid tumor as that in MTR state.

Adolescent↗

PubMedDate not supplied

Aggression, antisocial behavior, and substance abuse in survivors of pediatric cancer: possible protective effects of cancer and its treatment.

OBJECTIVE: To examine aggression, antisocial behavior, and substance abuse in young adult survivors of pediatric cancer (PCS) relative to case control peers (CC). METHODS: We obtained self-reports of current aggression, antisocial behavior, and lifetime substance use from 26 PCS (time off-treatment, M: = 56 months) and 26 CC using the Antisocial Behavior Checklist and the Drinking and Drug History. A report of current aggression and antisocial behavior also was obtained from primary caregivers using the Child Behavior Checklist. RESULTS: PCS self-reported significantly less illegal drug use and experimentation than CC. No significant differences emerged between groups for use of alcohol and tobacco nor for aggression and antisocial behavior. CONCLUSIONS: PCS are functioning as well as, or better than, CC in terms of aggression, antisocial behavior, and substance abuse. However, given the compromised health status of survivors, efforts should focus on further reduction of drug-related risk behaviors that may amplify organ damage or increase risk for further malignancies in this population.

Adolescent↗

PubMed1982

Pharmacokinetic study of indicine N-oxide in pediatric cancer patients.

Pharmacokinetics of the experimental antitumor agent indicine N-oxide were investigated in a group of 23 pediatric cancer patients. Plasma elimination of indicine N-oxide was best described by a two-compartment open model. The mean plasma distribution phase half-life, plasma elimination phase half-life, and plasma clearance were 8 min, 84 min, and 62 ml/min/m2 (2.1 ml/min/kg), respectively. One patient with renal impairment had an abnormally long plasma elimination phase half-life (275 min) and reduced plasma clearance (17 ml/min/m2). Plasma elimination phase half-life values increased and plasma clearance values decreased with increasing age of the pediatric patients. Plasma elimination of indicine N-oxide was more rapid in this group of children than in adults who had previously received the drug.

Adolescent↗

PubMed1986

Long-term use of indwelling multipurpose silastic catheters in pediatric cancer patients treated with aggressive chemotherapy.

We studied the complications related to the use of 53 multipurpose silastic catheters (MSC) placed in 46 pediatric cancer patients over a 1-year period. We documented the longest duration of catheter placement in the pediatric oncology literature. There were 7,650 Broviac days (range, 9 to 365 days; mean, 163 days) with 255 patient months of catheter use and a mean of 5.5 months per catheter. Of the 53 MSCs, 90% were Broviacs (72% adult size, 18% pediatric size) and 10% Hickman. There were 23 episodes of bacteremias or 0.31 episodes per 100 days of catheter use. Coagulase-negative staphylococci were isolated in 20% of the episodes of bacteremia. Only 34% had an absolute granulocyte count (AGC) (Polymorphonuclear cells [PMN] + band cells) less than 500 in the 23 MSCs with bacteremia. Ten percent were removed: 4% for mechanical problems, 6% for bacteremia unresponsive to appropriate antibiotic therapy. There were no deaths related to bacteremia, embolism, or vascular damage. This study demonstrated that despite the recent use of more aggressive immunosuppressive therapy, the incidence of MSC bacteremias was 43%, similar to earlier National Cancer Institute studies (39%) American Society of Clinical Oncology, (abstract C-219, 1982). Based on these findings, we have currently modified our MSC care and have recently throughout the past 6 months reduced our infectious complication rate by 50%.

Adolescent↗

PubMed1992

The incidence of pediatric cancer in Florida, 1981 to 1986.

Incidence rates for pediatric (ages, 0 to 14 years) cancer in the state of Florida were produced for the period 1981 to 1986 and compared with national data to investigate variations in pediatric cancer incidence. Overall, Florida had an incidence rate of 12.77 per 100,000; this was not significantly higher than expected based on national rates (standardized incidence ratio, 1.0; 95% confidence interval, 0.9 to 1.0). Compared with national rates, whites residing in Florida had an increased rate of acute lymphocytic leukemia and decreased rate for soft tissue sarcomas (other than rhabdomyosarcoma), "other leukemias," and "other" cancers. Nonwhites residing in Florida had increased rates for soft tissue sarcomas (other than rhabdomyosarcoma) and decreased rates of "other" cancers. Boys in Florida had increased rates for retinoblastoma and acute lymphocytic leukemia and decreased rates for "other leukemias" and "other" cancers. Rates for girls were decreased for neuroblastoma and "other leukemias."

Adolescent↗

PubMed1995

Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery.

Cycling intensive chemotherapy currently used to treat pediatric solid tumors induces severe neutropenia. Prolonged neutropenia is a major risk factor for septic death which occurs in up to 5% of febrile or septic neutropenic episodes. We treated 18 neutropenic pediatric cancer patients (eight females, 10 males) during 30 febrile and/or septic episodes with single daily doses of E. coli-derived non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rh-GM-CSF, 5 micrograms per kg of body weight). The cytokine was administered for a median period of 6.5 days (2-12 days). Analysis of circulating hematopoietic progenitor cells was performed at day 1 (baseline) and day 5 of rh-GM-CSF treatment and included flow cytometric CD34 analysis as well as the methylcellulose-based clonogenic assay. Prompt hematopoietic recovery and resolution of septic problems was observed in all children. The counts of leukocytes (WBC), absolute neutrophils (ANC), and platelets (PLT) rose above 1,000/microL, 1,000/microL, and 50,000/microL within 4 days (0-9), 5.5 days (2-13), and 6 days (0-14), respectively. Faster granulocyte recovery and improved recruitment of circulating hemopoietic precursors was observed in children with detectable amounts (> 0.1%) of CD34-positive mononuclear cells prior to rh-GM-CSF treatment. We conclude that, to some extent, the efficacy of rh-GM-CSF treatment in neutropenic cancer patients is influenced by the hematopoietic recovery status on the progenitor cell level. Although they respond more slowly to the treatment, patients without circulating CD34-positive progenitor cells may gain most from growth factor therapy. Rh-GM-CSF can be safely administered to febrile and/or septic neutropenic children treated for cancer.

Adolescent↗

PubMed2001

Trauma and personality correlates in long-term pediatric cancer survivors.

To explore the relationship between PTSD and trauma-spectrum symptoms, including personality and functional correlates, in long term pediatric cancer survivors (N = 40), we assessed these constructs with a structured interview for PTSD, a clinical interview, and self-report questionnaires. Thirty-five out of 40 participants (88%) currently met at least one trauma symptom at a functionally significant level. These survivors demonstrate high levels of restraint and low levels of distress, representative of a repressive adaptive style. After more than 5 years since treatment completion, the relatively high levels of current trauma-spectrum symptoms may reflect the long-term deleterious impact of childhood cancer.

Adaptation, Psychological↗

PubMed2005

Psychological distress and the impact of social support on fathers and mothers of pediatric cancer patients: long-term prospective results.

OBJECTIVE: To explore the effects of social support on psychological distress of parents of pediatric cancer patients using a prospective design over a 5-year period. METHODS: Parents of children diagnosed with cancer participated at diagnosis (T1), 6 months (T2), 12 months (T3), and 5 years later (T4). Instruments The General Health Questionnaire and the Social Support List (SSL) measuring amount of support, (dis)satisfaction with support, and negative interactions were administered. RESULTS: Psychological distress and amount of support received decreased significantly from diagnosis to T4. No significant change in (dis)satisfaction with support and negative interactions was found. Social support variables did not show any concurrent or prospective significant effect on mothers' distress at T4. Dissatisfaction with support showed a significant unique concurrent effect on fathers' distress at T4 and negative interactions had a prospective unique effect. CONCLUSIONS: Dissatisfaction with support and negative interactions that fathers experienced significantly affected their levels of psychological distress. No such effect was found for mothers.

Adult↗