Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 87
Filter
1.
ESMO Open ; 6(5): 100250, 2021 10.
Article in English | MEDLINE | ID: mdl-34562750

ABSTRACT

BACKGROUND: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). PATIENTS AND METHODS: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. RESULTS: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan-Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. CONCLUSIONS: The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755).


Subject(s)
Antineoplastic Agents , Bone Neoplasms , Osteosarcoma , Adolescent , Antineoplastic Agents/adverse effects , Bone Neoplasms/drug therapy , Child , Humans , Iodine Radioisotopes/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Osteosarcoma/drug therapy , Phenylurea Compounds , Quinolines , Young Adult
2.
Ann R Coll Surg Engl ; 102(1): 67-70, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31508997

ABSTRACT

BACKGROUND: Congenital mesoblastic nephroma is a rare disease. Treatment is surgical in the first instance. Chemotherapy has traditionally been thought not to have a role. Recent literature suggests a 50% mortality rate for recurrent/metastatic disease. MATERIALS AND METHODS: This study is a retrospective case review of prospectively collected data. Demographics, histopathology, treatment, outcomes and follow up were reviewed. RESULTS: Nine patients, 6 male and 3 female, were included. The median age at presentation was one month (range 0-7 months); follow-up was for a median of 21.5 months (range 16-79 months). Two patients had mixed and classical subtypes and the other five had the cellular subtype. Surgery was completed by an open procedure in eight patients and laparoscopically in one. There were three recurrences; two were local and one was pulmonary. Recurrences were treated with a combination of chemotherapy, radiotherapy and surgery. One patient with recurrent disease died from acute-on-chronic respiratory failure secondary to lung irradiation but was disease free. The other eight are disease free, alive and well with no sequelae at latest follow-up. CONCLUSIONS: Surgery remains the mainstay of management with chemo- and radiotherapy reserved for unresectable tumours or adjuvant management of recurrent disease. Specimen-positive margins are not an indication for instituting chemotherapy. The tyrosine kinase pathway seems to be a potential target for future chemotherapeutic agents although it is too early to assess how that will impact on the management of congenital mesoblastic nephroma.


Subject(s)
Kidney Neoplasms/congenital , Nephroma, Mesoblastic/congenital , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy/mortality , Disease-Free Survival , Female , Humans , Infant , Infant, Newborn , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Laparoscopy/statistics & numerical data , Lung Neoplasms/secondary , Male , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/therapy , Nephroma, Mesoblastic/mortality , Nephroma, Mesoblastic/therapy , Prospective Studies , Retrospective Studies , Treatment Outcome
3.
Clin Exp Dermatol ; 43(6): 713-717, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29744913

ABSTRACT

Cartilage-hair hypoplasia (CHH) is an autosomal recessive chondrodysplasia characterized by short-stature, sparse hair and impaired cellular immunity. We describe a young girl who was diagnosed with CHH based on the findings of recurrent infections, short stature with metaphyseal chondrodysplasia, and a confirmed bi-allelic RMRP gene mutation. At 13 years, the patient developed an Epstein-Barr virus (EBV)-driven lymphoproliferative disorder involving the lung, which responded partially to chemotherapy. Simultaneously, she developed multiple indurated plaques involving her face, which had histological findings of granulomatous inflammation and EBV-associated low-grade lymphomatoid granulomatosis. The patient received a matched unrelated peripheral blood stem cell transplant at 15 years of age, and her immunological parameters and skin lesions improved. Lymphomatoid forms of granulomatosis and cutaneous EBV-associated malignancies have not been described previously in CHH. This case highlights the possibility of EBV-associated cutaneous malignancy in CHH.


Subject(s)
Hair/abnormalities , Hirschsprung Disease/complications , Immunologic Deficiency Syndromes/complications , Lung Neoplasms/complications , Lung/pathology , Lymphomatoid Granulomatosis/complications , Osteochondrodysplasias/congenital , Skin Neoplasms/complications , Adolescent , Female , Herpesvirus 4, Human/isolation & purification , Hirschsprung Disease/therapy , Humans , Immunologic Deficiency Syndromes/therapy , Lung/virology , Lung Neoplasms/pathology , Lymphomatoid Granulomatosis/pathology , Osteochondrodysplasias/complications , Osteochondrodysplasias/therapy , Primary Immunodeficiency Diseases , Stem Cell Transplantation
4.
Pediatr Blood Cancer ; 61(3): 442-5, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24019263

ABSTRACT

BACKGROUND: The prognosis for patients with nonpulmonary metastatic Ewing sarcoma remains poor with survival in the order of 15-20%. The need to introduce effective new agents into clinical practice is clear. Based on a preclinical rationale of responses in xenografts and backed by a phase I study in children, the Euro-E.W.I.N.G consortium planned a phase II window study of irinotecan in newly diagnosed high risk metastatic patients with Ewing sarcoma. PROCEDURES: Patients were recruited between April 2004 and December 2007. Two courses of irinotecan were administered at a dose of 600 mg/m(2) as a 1 hour infusion at 21 day intervals. Response evaluation was determined after the second course of treatment by radiological assessment of primary and metastatic sites and, where appropriate bone marrow sampling. RESULTS: Twenty-three patients were recruited. Two patients were deemed inevaluable for response. Five patients (24%) demonstrated a partial response. Grade 3 or 4 diarrhoea was seen in 4/43 course of treatment and was managed with loperamide. CONCLUSIONS: This is the first report of single agent irinotecan activity in an untreated population of patients with Ewing sarcoma. In common with other paediatric tumours and other camptothecin analogues such as topotecan, single agent activity is only modest. The exact role for the use of irinotecan in patients with ES, dose schedule and combinations with other agents still requires further investigation.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Bone Neoplasms/drug therapy , Camptothecin/analogs & derivatives , Sarcoma, Ewing/drug therapy , Adolescent , Camptothecin/adverse effects , Camptothecin/therapeutic use , Child , Humans , Irinotecan , Risk
5.
Pediatr Transplant ; 18(1): 52-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24341552

ABSTRACT

To compare the incidence of acute histologically proven rejection in children who have had a liver transplant for hepatoblastoma with a control group of children transplanted for biliary atresia (EHBA). A retrospective case notes based study was performed. Twenty patients were identified with hepatoblastoma who were transplanted at a single unit between 1991 and 2008. These were matched as closely as possible for age, gender, year of transplant and type of immunosuppression used to the control group transplanted for biliary atresia (n = 60). There was a significant decrease in rate of acute rejection as assessed by the rejection activity index (RAI) in the hepatoblastoma group (75% vs. 50%, respectively, p < 0.04). Chronic rejection was rare in both groups, but twice as common in the biliary atresia group. Equal levels of immunosuppression were achieved in both groups. Renal function was noted to be reduced one yr post-transplant in both groups, as previously reported. A modified immunosuppression regimen could be considered in children with hepatoblastoma undergoing liver transplantation.


Subject(s)
Graft Rejection/epidemiology , Hepatoblastoma/therapy , Liver Neoplasms/therapy , Liver Transplantation , Biliary Atresia/therapy , Child , Child, Preschool , Female , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Male , Retrospective Studies , Treatment Outcome
6.
Ecancermedicalscience ; 5: 210, 2011.
Article in English | MEDLINE | ID: mdl-22276053

ABSTRACT

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

7.
Paediatr Perinat Epidemiol ; 24(5): 470-8, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20670227

ABSTRACT

Malignant bone tumours in the paediatric age group (0-14 years) are uncommon; various aetiological theories exist and few reports of incidence, age and sex distributions have been published. We examined the incidence of childhood malignant bone tumours in one large single region of the UK over an extended period of 50 years. The West Midlands specialist regional children's tumour registry holds data on all malignancies and benign brain tumours in children under 15 years in the West Midlands region, which has a population of around 1 million children. Demographic and clinical data have been abstracted and diagnoses reviewed by a panel of expert pathologists. During the period 1957-2006, 259 cases of malignant paediatric bone tumours were diagnosed. There were 153 osteosarcomas, 78 Ewing sarcomas and 28 other primary bone tumours. The overall age standardised rate was 4.66, with no increase over time, although there was a significant increase in the incidence of Ewing sarcomas in the period 1965-92. Sixty-eight per cent of tumours were in patients over 10 years, whereas the incidence in patients under 10 years showed a non-significant increase. Survival rates increased dramatically post-chemotherapy introduction, with Ewing sarcoma demonstrating better survival overall. This is a large study giving an overview of malignant bone tumours in the childhood population of a single region over an extended period, showing results consistent with national reports. It also examines late effects, which were mostly mobility/orthopaedic, although almost one-fifth of patients had cardiac problems and five went on to develop second malignancies.


Subject(s)
Bone Neoplasms/therapy , Sarcoma, Ewing/therapy , Adolescent , Bone Neoplasms/epidemiology , Child , Child, Preschool , Female , Humans , Incidence , Infant , Male , Proportional Hazards Models , Sarcoma, Ewing/epidemiology , Survival Rate , Treatment Outcome , United Kingdom
8.
Pediatr Blood Cancer ; 48(2): 160-4, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16317755

ABSTRACT

PURPOSE: The aims were to identify and test the significance of specific factors associated with risks for anaesthesia in children with mediastinal tumours. PATIENTS AND METHOD: Clinical information was retrospectively collected from the records of 63 children presented with mediastinal tumour (1964-2002) in a regional Paediatric Oncology centre and correlated with the type and outcome of anaesthesia, using non-parametric analyses. RESULTS: Thirteen patients had local anaesthesia or sedation for diagnostic procedures and none developed any complication. Fifty children received general anaesthesia (GA) for diagnostic investigations or tumour resection. Two patients were excluded from the analysis because of treatment prior to GA. Problems with intubation, ventilation and cardiovascular collapse were encountered in 7 of 48 (15%) patients and this resulted in tracheostomy in one patient and death in 2 other cases. When compared with the 41 uncomplicated cases, the presence of at least 3 respiratory symptoms/signs, tracheal and vascular compression, and infection significantly increased the risk of GA. Of these, tracheal compression remained the strongest predictive factor. CONCLUSIONS: Decision to postpone GA should be considered if all these risk factors (tracheal compression, vascular compression, the presence of at least three respiratory symptoms/signs) are present in the same patient.


Subject(s)
Anesthesia, General/adverse effects , Mediastinal Neoplasms/physiopathology , Adolescent , Anemia/complications , Child , Child, Preschool , Female , Humans , Infant , Infections/complications , Male , Mediastinal Neoplasms/diagnosis , Respiratory Insufficiency/etiology , Retrospective Studies , Risk Factors , Shock/etiology , Tracheostomy
9.
Pediatr Blood Cancer ; 48(4): 473-6, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16078220

ABSTRACT

A teenage boy presented with a CD30-positive anaplastic large cell lymphoma (ALCL) affecting his scapula and was successfully treated with chemotherapy. His clinical features and outcome were compared with other cases described in the literature. A further review of 11 ALCL cases with bony involvement treated in the UK since 1990, including two with primary bone disease, did not suggest an unfavorable treatment outcome. This finding will need to be confirmed by further study on a larger patient cohort with primary bone ALCL.


Subject(s)
Bone Neoplasms/pathology , Lymphoma, Large-Cell, Anaplastic/pathology , Scapula/pathology , Activin Receptors, Type II/analysis , Activin Receptors, Type II/genetics , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/analysis , Biomarkers, Tumor/genetics , Bone Neoplasms/chemistry , Bone Neoplasms/diagnosis , Bone Neoplasms/drug therapy , Bone Neoplasms/epidemiology , Bone Neoplasms/genetics , Child , Child, Preschool , Cohort Studies , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Infant , Ki-1 Antigen/analysis , Lymphoma, Large-Cell, Anaplastic/chemistry , Lymphoma, Large-Cell, Anaplastic/diagnosis , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/epidemiology , Lymphoma, Large-Cell, Anaplastic/genetics , Magnetic Resonance Imaging , Male , Methotrexate/administration & dosage , Prognosis , Remission Induction , Treatment Outcome , United Kingdom/epidemiology
10.
Pediatr Hematol Oncol ; 22(3): 257-61, 2005.
Article in English | MEDLINE | ID: mdl-16020110

ABSTRACT

Clear cell sarcoma of the kidney (CCSK) has been classified as high risk tumour in the previous UK and international Wilms tumor studies. The current Society of Paediatric Oncology (SIOP) trial, UK version, advocates chemotherapy including doxorubicin prior to nephrectomy. Pathological staging and histology of the resected tumor are then applied to determine the extent and intensity of the postoperative therapy. We describe an unusual case with a trilobed tumor and debate the appropriate postoperative management.


Subject(s)
Kidney Neoplasms/pathology , Sarcoma, Clear Cell/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Doxorubicin/therapeutic use , Humans , Infant , Kidney Neoplasms/drug therapy , Kidney Neoplasms/surgery , Male , Neoplasm Staging , Nephrectomy/methods , Postoperative Care/methods , Sarcoma, Clear Cell/drug therapy , Sarcoma, Clear Cell/surgery
11.
Eur J Cancer ; 40(12): 1886-92, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15288291

ABSTRACT

Childhood cancer is a relatively rare disease, representing just 1% of all malignancies. Within Europe, this represents some 12,000 new cases each year, with approximately 1600 a year in the United Kingdom and 1800 in France. International collaboration in phase III trials of childhood cancer has been the norm for many years, traditionally within Europe, but, largely because of organisational considerations, phase I and II trials have only been conducted on a national basis. With overall cure rates in the region of 70%, relatively few children are available for these early drug trials. Access to new drugs is also a major problem. Against this background, a United Kingdom (UK)/French 'new agent' collaboration was established, expanding subsequently into a wider European grouping. This paper documents the history of that collaboration, the outcomes and future challenges.


Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Child , Clinical Trials, Phase I as Topic , Clinical Trials, Phase II as Topic , Drug Design , Europe , Forecasting , Humans , International Cooperation , Multicenter Studies as Topic
12.
Pediatr Blood Cancer ; 43(3): 257-60, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15266410

ABSTRACT

BACKGROUND: To investigate the incidence, clinical characteristics and survival of malignant tumours of the gastrointestinal tract in children in the West Midlands in Britain over a 44-year span time, to identify any change over this period and to compare the data with the world literature. PROCEDURE: Retrospective population based study. Fifty-seven patients were identified from the records of the West Midlands Regional Children's Tumour Registry. Age-standardised incidence rates were calculated using the world standardised population method. Statistical tests used were the Log rank test and survival curves were produced using the Kaplan-Meier method. RESULTS: The age-standardised incidence of overall gut tumours during the period 1957-2000 was 1.10/million/year. The age standardised incidence of non-Hodgkin lymphoma (NHL) was calculated as 0.9/million/year and for adenocarcinoma 0.14/million/year. CONCLUSION: Malignant tumours of the gastrointestinal tract remain rare in children. No changing trends in incidence were observed over the 44-year period. NHL was the commonest malignancy overall and of the small bowel while equal number of adenocarcinoma and NHL were identified in the large bowel. There was no significant difference in survival between sexes, site and age groups in both NHL and adenocarcinoma. Survival has improved over the last four decades for NHL patients but remains poor for the adenocarcinoma patients.


Subject(s)
Gastrointestinal Neoplasms/epidemiology , Adolescent , Child , Child, Preschool , Data Collection , England , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/mortality , Humans , Incidence , Male , Organ Specificity , Survival Analysis
13.
Pediatr Hematol Oncol ; 20(6): 439-44, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14631617

ABSTRACT

The authors discuss the morbidity associated with viridans streptococcus bacteremia, and its implications on the choice of antibiotics used as prophylaxis and treatment. They retrospectively studied the case notes of 38 children who were being treated for various malignant conditions in their unit and developed 40 episodes of bacteremia with viridans streptococci between October 1995 and January 1999. Viridans streptococci were the third commonest blood culture isolate during this period, after coagulase-negative staphylococci and Staphylococcus aureus. The majority of the isolates were Streptococcus mitis (55%). Others were S. sanguis (25%), S. oralis (12.5%), S. salivarius (5%), and S. acidominimus (2.5%). Twenty-five percent of the patients had been treated with regimens that included cytosine arabinoside, 60% were receiving prophylactic co-trimoxazole, and 87.5% were neutropenic. Thirty percent of patients had abnormal chest X-rays, and 15% were hypotensive; 2 patients required admission to the intensive care unit. Initial antibiotic therapy was changed because of failure of clinical response in 60% of cases, despite the infecting organism being sensitive in vitro. This study confirms the importance of viridans streptococci as a cause of bacteremia in pediatric hematology and oncology patients, leading to significant morbidity. Further work is required to establish the optimal treatment for viridans streptococcus bacteremia.


Subject(s)
Antineoplastic Agents/adverse effects , Bacteremia/microbiology , Neoplasms/drug therapy , Streptococcal Infections/microbiology , Viridans Streptococci/isolation & purification , Adolescent , Bacteremia/epidemiology , Bacteremia/etiology , Child , Child, Preschool , Drug Resistance , Escherichia coli Infections/epidemiology , Female , Humans , Immunocompromised Host , Infant , Male , Neutropenia/chemically induced , Retrospective Studies , Species Specificity , Staphylococcal Infections/epidemiology , Streptococcal Infections/epidemiology , Streptococcal Infections/etiology , Viridans Streptococci/drug effects
14.
Pediatr Hematol Oncol ; 20(1): 55-63, 2003.
Article in English | MEDLINE | ID: mdl-12687754

ABSTRACT

A 4-year-old girl developed right metachronous Wilms tumor 2 years after completing treatment for a left-sided stage I Wilms tumor. The original treatment included 7 weeks of chemotherapy, delayed nephrectomy, and another 3 weeks of chemotherapy. The metachronous tumor on the right side extended into the inferior vena cava and right atrium. She developed pulmonary embolism as a result. She received chemotherapy and developed liquifaction of the tumor and toxic shock. She also had surgery. The patient is alive 3 years after the original diagnosis and 10 months after the relapse. The authors report this unusual case and discuss whether these cases can be identified early.


Subject(s)
Neoplasms, Second Primary/complications , Pulmonary Embolism/etiology , Wilms Tumor/complications , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child, Preschool , Female , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/therapy , Nephrectomy , Wilms Tumor/diagnosis , Wilms Tumor/therapy
15.
J Pediatr Surg ; 37(2): 240-5, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11819207

ABSTRACT

BACKGROUND: Liver transplantation now is proposed for managing selected hepatoblastoma cases. Indications are not yet well defined. METHODS: The case records of 34 children with hepatoblastoma treated over a period of 10 years (1991 to 2000) were reviewed retrospectively. RESULTS: All patients benefited from preoperative chemotherapy. Twenty patients underwent major hepatic resections. Twelve patients, in absence of residual metastasis, underwent liver transplant because the tumour remained unresectable after chemotherapy. Two patients who presented with recurrence after a right hepatectomy, benefited from transplant as a second option. Two other patients did not undergo surgery because of widespread disease or resistance to chemotherapy. Disease-free survival rates were 95% after surgical resection, 100% when primary transplant was performed in patients with good response to chemotherapy, 60% after transplantation in patients with poor response to chemotherapy, 50% in patients with transplant as second option, and 0% in patients not undergoing surgery. CONCLUSIONS: Transplantation is a potentially curative option for unresectable hepatoblastoma when chemosensitive (decrease in alpha-fetoprotein and decrease in tumour size). In this context, also favourable cases with good response but difficult resections with doubtful margins of resection may best be proposed for primary transplantation. Patients with recurrent or resistant disease are not good candidates.


Subject(s)
Hepatectomy/methods , Hepatoblastoma/surgery , Liver Neoplasms/surgery , Liver Transplantation/methods , Antineoplastic Agents/therapeutic use , Child, Preschool , Combined Modality Therapy/methods , Disease-Free Survival , Female , Hepatoblastoma/drug therapy , Humans , Infant , Liver Neoplasms/drug therapy , Male , Recurrence , Reoperation , Retrospective Studies , Treatment Outcome
16.
Med Pediatr Oncol ; 38(2): 98-103, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11813173

ABSTRACT

BACKGROUND: Despite the current widespread use of prophylactic G-CSF in children with solid tumours and leukaemia, its effectiveness has not been clearly demonstrated. This randomised study evaluates the role of G-CSF given after a 5-day intensification block in children with acute lymphoblastic leukaemia (ALL). PROCEDURE: Forty-six children with ALL or T-Cell non-Hodgkins lymphoma (NHL) treated on MRC ALL 97, UKALL XI or UKCCSG 9504 NHL protocols were randomised to receive granulocyte colony-stimulating factor following either the first or the second block of intensive chemotherapy in a cross-over study to determine if the prophylactic administration of G-CSF could reduce the rate of readmission to hospital for management of febrile neutropenia. RESULTS: There was a statistically significant difference in the rate of hospital admission in the group receiving prophylaxis, with 34 of 46 being admitted, compared to 42 of 46 patients in the control arm (74 vs. 91%; P=0.0386). There were no differences found in duration of hospital admission, haematological toxicity, neutrophil recovery or duration of supportive care between the two groups. There was no demonstrable cost benefit derived from the prophylactic administration of G-CSF. CONCLUSIONS: This study shows that the prophylactic administration of G-CSF following intensification chemotherapy for childhood ALL and T-NHL produces a significant reduction in the rate of readmission to hospital for the management of febrile neutropenia.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Lymphoma, T-Cell/drug therapy , Neutropenia/prevention & control , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Child , Child, Preschool , Cost-Benefit Analysis , Cross-Over Studies , Female , Filgrastim , Granulocyte Colony-Stimulating Factor/economics , Humans , Infant , Male , Neutropenia/chemically induced , Neutropenia/epidemiology , Patient Readmission/economics , Patient Readmission/statistics & numerical data , Prospective Studies , Recombinant Proteins , United Kingdom/epidemiology
17.
Cancer Genet Cytogenet ; 130(2): 133-40, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11675134

ABSTRACT

The pediatric tumor neuroblastoma is characterized by a very variable, and at times unpredictable, pattern of clinical behavior, ranging from a benign localized tumor to an aggressive malignancy with poor prognosis. Standard clinical and pathological assessments do not always differentiate reliably between tumor subtypes and, therefore, genetic markers are now playing an increasingly important role in treatment decisions. MYCN oncogene amplification, for example, provides a useful marker of poor prognosis. However, less than one-half of all patients who present with, or who later develop, metastatic disease show MYCN amplification. Consequently, the identification of characteristic patterns of genetic alteration in the remaining tumors is of importance. In this report, we describe two new cell lines that we have established from metastatic, non-MYCN amplified, advanced stage neuroblastomas. These cell lines show a number of features in common, including unbalanced translocation between 11q and 17q, loss of 3p, 4p and 11q and gain of 17q. Therefore, they provide a valuable resource for the characterization of genetic pathways leading to aggressive tumor growth in non-MYCN amplified neuroblastomas.


Subject(s)
Chromosomes, Human, Pair 11 , Chromosomes, Human, Pair 17 , Genes, myc/genetics , Genetic Markers , Neuroblastoma/genetics , Translocation, Genetic , Adrenal Gland Neoplasms/genetics , Cells, Cultured , Child, Preschool , Chromosome Aberrations , Chromosome Banding , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 3 , Cytogenetic Analysis , Humans , Immunohistochemistry , Male , Microsatellite Repeats/genetics , Phenotype , Prognosis , Tumor Cells, Cultured
19.
Tidsskr Nor Laegeforen ; 121(15): 1812-5, 2001 Jun 10.
Article in Norwegian | MEDLINE | ID: mdl-11464687

ABSTRACT

BACKGROUND: Ambulatory blood pressure measurements may be performed with manual or automatic devices. Such methods seem to be increasingly used for diagnosing conditions like "white coat hypertension" or abnormal variations in the 24-hour blood pressure profile. However, it is not yet known whether these patients are exposed to an increased risk of cardiovascular events. MATERIALS AND METHODS: This paper is a summary of systematic reviews (health technology assessment reports) of the performance and effectiveness of ambulatory blood pressure measurements for the diagnosis of hypertension. RESULTS: Ambulatory blood pressure measurements may be used during medical treatment for hypertension to control blood pressure, and patients using these measurements have been shown to reach the target blood pressure at lower medication levels than patients depending on blood pressure measurements in the surgery. INTERPRETATION: Widespread use of ambulatory blood pressure measurements in order to predict cardiovascular risk requires knowledge about diagnostic and prognostic performance. There are studies that address these concerns, but major weaknesses in study design limit their value. The lack of a consensus on reference values is also an impediment to the use of ambulatory blood pressure measurements.


Subject(s)
Blood Pressure Monitoring, Ambulatory/methods , Hypertension/diagnosis , Blood Pressure Monitoring, Ambulatory/economics , Blood Pressure Monitoring, Ambulatory/standards , Clinical Trials as Topic , Cost-Benefit Analysis , Humans , Prognosis , Randomized Controlled Trials as Topic , Reference Values
20.
Br J Cancer ; 84(8): 1029-35, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11308249

ABSTRACT

Pre-clinical studies indicate that cisplatin encapsulated in STEALTH((R))liposomes (SPI-77) retains anti-tumour activity, but has a much reduced toxicity, compared to native cisplatin. A phase I study was conducted to determine the toxicity and pharmacokinetics of SPI-77 administered to children with advanced cancer not amenable to other treatment. Paediatric patients were treated at doses ranging from 40 to 320 mg m(-2)by intravenous infusion every 4 weeks. Blood samples taken during, and up to 3 weeks after, administration and plasma and ultrafiltrate were prepared immediately. Urine was collected, when possible, for 3 days after administration. SPI-77 administration was well tolerated with the major toxicity being an infusion reaction which responded to modification of the initial infusion rate of SPI-77. Limited haematological toxicity and no nephrotoxicity were observed. No responses to treatment were seen during the course of this phase I study. Measurement of total plasma platinum showed that cisplatin was retained in the circulation with a half life of up to 134 h, with maximum plasma concentrations approximately 100-fold higher than those reported following comparable doses of cisplatin. Comparison of plasma and whole blood indicated that cisplatin was retained in the liposomes and there was no free platinum measurable in the ultrafiltrate. Urine recovery was less than 4% of the dose administered over 72 h. Results from this phase I study indicate that high doses of liposomal cisplatin can safely be given to patients, but further studies are required to address the issue of reformulation of liposomally bound cisplatin.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Cisplatin/pharmacokinetics , Neoplasms/drug therapy , Podophyllin/analogs & derivatives , Podophyllin/pharmacokinetics , Adolescent , Antineoplastic Agents/adverse effects , Area Under Curve , Child , Child, Preschool , Cholesterol/blood , Cisplatin/adverse effects , Cisplatin/blood , Dose-Response Relationship, Drug , Female , Humans , Infant , Lipids/blood , Lipoproteins, HDL/blood , Lipoproteins, HDL/drug effects , Lipoproteins, LDL/blood , Lipoproteins, LDL/drug effects , Liposomes , Male , Neoplasms/metabolism , Podophyllin/adverse effects , Podophyllin/blood , Podophyllotoxin/analogs & derivatives , Time Factors , Triglycerides/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...