Funda Corapcioglu

MONOTHERAPY WITH PIPERACILLIN/TAZOBACTAM VERSUS CEFEPIME AS EMPIRICAL THERAPY FOR FEBRILE NEUTROPENIA IN PEDIATRIC CANCER PATIENTS: A Randomized Comparison

The purpose of this study was to compare the efficacy, safety, and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia. A prospective randomized study in children and adolescent with cancer was conducted. Patients were randomly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h (maximum 4.5 g/dose) or cefepime 50 mg/kg every 8 h (maximum 2 g/dose). Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification. Cost of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile netropenic episodes (25 in the piperacillin/tazobactam group, 25 in the cefepime group) in 27 pediatric cancer patients were evaluated. The groups were comparable in terms of age, gender, body weight, primary diagnosis, disease status, initial neutrophil count, and duration of neutropenia. Microbiologically and clinically documented infection rate was 46%. There was no infection-related mortality in the study period. The treatment success of initial empirical therapy without modification was not different in the 2 groups (56% in piperacillin/tazobactam group and 48% in cefepime group). Anti-anaerobic drugs were added more frequently in the cefepime group. Duration of fever, neutropenia, treatment, and cost of therapy were not different in the treatment groups. Piperacillin/tazobactam monoterapy is as effective as cefepime monotherapy in febril neutropenia of pediatric cancer patients.

EVALUATION OF ANTHRACYCLINE-INDUCED EARLY LEFT VENTRICULAR DYSFUNCTION IN CHILDREN WITH CANCER: A Comparative Study with Echocardiography and Multigated Radionuclide Angiography

The study aimed to compare diastolic and systolic dysfunctions detected by echocardiography (ECHO) and multigated radionuclide angiography (MUGA) in patients with cancer in the first 3 months after anthracycline-comprising chemotherapy. Children with leukemia and solid tumors who had anthracycline-comprising chemotherapy were enrolled in the study. ECHO and MUGA were performed in all patients before the first chemotherapy course and in the first 3 month of completing anthracycline-comprising chemotherapy. Cumulative anthracycline doses per body surface were calculated. Left ventricular systolic and diastolic functions were measured by both techniques. Twenty-one patients with a median age of 6.9 ± 3.6 years were enrolled in the study. Mean cumulative anthracycline doses were equivalent to 276 ± 83 mg/m2 doxorubicin. After anthracycline chemotherapy, cardiac dysfunction was detected in 14 and 48% of the patients by ECHO and MUGA, respectively. All dysfunctions detected by ECHO were systolic, whereas 29% of the patients had diastolic and 38% of the patients had systolic dysfunction in MUGA study. Although the study group is small, MUGA seems more sensitive in detecting anthracycline-induced systolic and diastolic cardiac dysfunctions compared to ECHO.

Cefepime versus ceftazidime + amikacin as empirical therapy for febrile neutropenia in children with cancer: a prospective randomized trial of the treatment efficacy and cost.

The efficacy, safety, and cost of cefepime and ceftazidime + amikacin as empirical therapy in children with febrile neutropenia is compared. A prospective randomized study in children with cancer was conducted. Patients were randomly assigned to receive either cefepime 150 mg/kg/day or ceftazidime 150 mg/kg/day combined with amikacin 15 mg/kg/day. Treatment modification was defined as all the changes in the empirical antimicrobials after the first 72 h. Overall treatment success was defined as cure of febrile episode with or without modification. Costs of hospitalization, antimicrobial drugs, and supportive therapy were calculated. Fifty febrile netropenic episodes were evaluated. Infectious agents were microbiologically identified in 28% of episodes. The incidence of gram-negative and gram-positive isolates was equal. Overall treatment success was 100% and success of initial empirical therapy without modification was 52 and 40% in the cefepime and cefepime + amikacin groups, respectively. The response rate after glycopeptides were added to the regimen was 64 and 52% in the cefepime and cefepime + amikacin arms, respectively. Glycopeptide and antifungal drugs were added more frequently in the ceftazidime + amikacin group. Duration of fever, hospitalization, and antimicrobial drug administration were longer in the ceftazidime + amikacin arm. The costs of the antimicrobial drugs, hospitalization, and total cost were lower in the cefepime arm. Cefepime monotherapy is as effective as ceftazidime + amikacin combination in febrile neutropenia of pediatric cancer patients and must be preferred due to shorter defervescence of fever, shorter hospitalization, and lower therapy cost.

Pediatric and young adult nasopharyngeal carcinoma patients treated with preradiation Cisplatin and docetaxel chemotherapy.

PURPOSE To evaluate treatment results for pediatric and young adult (aged <21 years) patients with nonmetastatic nasopharyngeal carcinoma treated with neoadjuvant cisplatin + docetaxel and radiotherapy. METHODS AND MATERIALS Ten patients with nasopharyngeal carcinoma who received diagnoses between 2004 and 2007 were treated with four cycles of cisplatin 100 mg/m(2) + docetaxel 75 mg/m(2) on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. RESULTS The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. CONCLUSION As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma.

Hepatic Adenomatosis in a 7-Year-Old Child Treated Earlier With a Fontan Procedure

Patients who undergo a Fontan procedure experience some degree of liver disease. Hemodynamic changes such as central venous hypertension, depressed dynamic cardiac output, and late ventricular dysfunction combined with long-standing hypoxia preceding the Fontan procedure all are recognized risk factors for hepatic injury. The histopathologic changes associated with cardiac hepatopathy include chronic passive congestion, centrilobular necrosis, and cardiac cirrhosis. However, hepatic adenoma and hepatic adenomatosis (HA) are not well-known pathologies during the course of cardiac hepatopathy. This study focused on a 7-year-old girl with chronic hepatic changes and HA who had undergone a Fontan procedure. Hepatic adenomatosis was diagnosed on the basis of magnetic resonance imaging (MRI) and MRI-guided liver biopsy. To the best of the authors’ knowledge, this case involved the youngest patient with hepatocellular adenomatosis documented in the literature. It was a unique case because the patient experienced HA after a Fontan procedure.

RESPONSE TO RITUXIMAB AND PREDNISOLONE FOR OPSOCLONUS-MYOCLONUS-ATAXIA SYNDROME IN A CHILD WITH GANGLIONEUROBLASTOMA

Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurobehavioral paraneoplastic disorder in children with neuroblastic tumors. The neurologic symptoms are generally treated with a number of immunosupressive and immunomodulating agents. A 4-year-old previously healthy male patient was admitted to the authors’ center with progressive ataxia, gait disturbance, diffuculty of speech, and opsoclonus. He had a diagnosis of ganglionueroblastoma at the thoracal paraspinal region. Following surgey, the patient received IVIG and prednisolone but his cerebellar symptoms progressed. Rituximab therapy was started and continued for total 8 weeks without any side effect. The authors observed excellent neurologic response in the patient at the 4th week of treatment. Rituximab is a new, promising, and safe therapy for OMA syndrome in children with neuroblastoma.

Gorham-Stout Syndrome with Chylothorax in a Six-Year-Old Boy

Gorham-Stout syndrome, also called “disappearing bone disease, diffuse cystic angiomatosis of bone, disseminated lymphangiomatosis, Gorham’s vanishing bone disease, phantom bone disease or idiopathic massive osteolysis, is a rare disease of unknown etiology and pathogenesis. It is characterized by rapidly progressive localized massive osteolysis associated with proliferation of vascular structures of benign origin in which the absence of new bone formation is representative. When it is complicated by chylothorax, the prognosis is poor. The authors report a 6-year-old boy with Gorham-Stout syndrome who presented with pleural effusion showing features of chylothorax, who responsed poorly to currently available therapeutic modalities.

Posttraumatic stress disorder and risk factors in parents of children with a cancer diagnosis.

The purpose of this study was to determine the prevalence of posttraumatic stress disorder (PTSD) in parents of children with cancer. Five questionnaires were administered to 104 parents, including a sociodemographic questionnaire, a traumatic events check list, the Structured Clinical Interview for DSM-IV PTSD and Major Depressive Disorder modules, and the self-rating instrument General Health Questionnaire-12. The prevalence of PTSD was 34.6%. The statistically significant tendency to develop PTSD were found in the female gender, better educational status, death of a loved one, previous history of psychiatric disorder, having a child with poorer prognosis, and the presence of radiotherapy in childs treatment. The vulnerable parents must receive psychosocial support.

A PROSPECTIVE RANDOMIZED TRIAL OF THE ANTIEMETIC EFFICACY AND COST-EFFECTIVENESS OF INTRAVENOUS AND ORALLY DISINTEGRATING TABLET OF ONDANSETRON IN CHILDREN WITH CANCER

Orally disintegrating tablet (ODT) of ondansetron is a new formulation, which instantaneously disintegrates and disperses in the saliva without need for ingestion a liquid. This makes the formulation suitable for administration in children. The objective of this study was to compare the relative efficacy and cost of ODT and intravenous (IV) formulation of ondansetron in controlling nausea and vomiting in children receiving chemotherapy regimens without cisplatin. This prospective randomized trial was performed in a single institution to compare ODT and IV formulation of ondansetron for the prevention of acute emesis in a group of 22 children. Study agents were administered 30 min before chemotherapy and 12 hourly after chemotherapy (5 mg/m2 IV or 4–8 mg oral according to body surface area in 56 and 39 courses, respectively). After randomization, IV formulation was administered to some children instead of ODT due to unavaibility of this formulation. Complete and major control of emesis was obtained in 92% of patients in the IV group and 93% of patients in the ODT group. In 56 courses with grade III–IV emetogenicity, complete response rates were not different between the two treatment arms. In the courses without corticosteroids complete response rates were not also different between the two arms. The mean costs per successfully controlled courses were 121.3 USD for the IV formulation whereas 63.2 USD for the ODT formulation. The results of this study confirmed that ODT formulation of ondansetron is a safe, well-tolerated, and cost-effective antiemetic for children during non-cisplatin-containing moderately and highly emetogenic chemotherapy.

TREATMENT OF WILMS TUMOR: A Report from the Turkish Pediatric Oncology Group (TPOG)

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. Methods and patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III–IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II–IV UH tumors, VCR + Act-D + ADR + etoposide + RT. Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases ≤2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.