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Biomedical subjects

M J Coppes

Publications and source records attributed to M J Coppes.

At least 37 records · Page 2Linked to original sources
PubMed1999

Open-label comparison of the antiemetic efficacy of single intravenous doses of dolasetron mesylate in pediatric cancer patients receiving moderately to highly emetogenic chemotherapy.

BACKGROUND: Nausea and vomiting are among the most unpleasant adverse side effects of cancer therapy. PROCEDURE: An open-label dose-escalation study was conducted to assess the appropriate intravenous dose of dolasetron for pediatric patients undergoing chemotherapy. Patients received dolasetron in single intravenous doses of 0.6 (n = 10), 1.2 (n = 12), 1.8 (n = 12), or 2.4 (n = 12) mg/kg 30 min before receiving emetogenic chemotherapy. Pharmacokinetic parameters were evaluated at each dose level and efficacy was evaluated over the first 24 hr following the administration of dolasetron. RESULTS: A complete response was achieved in 10% of patients given 0.6 mg/kg, 25% of patients given 1. 2 mg/kg, 67% of patients given 1.8 mg/kg, and 33% of patients given 2.4 mg/kg. Peak plasma concentrations (Cmax) were observed between 0. 33 and 0.75 hr following dolasetron infusion. Cmax and area under plasma concentration-time (AUC) increased with larger doses of dolasetron, while terminal disposition half-life (t1/2) and apparent clearance (Clapp) were not significantly changed with respect to dose. For 1.8-mg/kg dolasetron, the t1/2 was 4.98 hr and the maximum plasma concentration (tmax) 0.47 hr. Adverse events were mild to moderate. No serious events occurred. Conclusions. This study suggests that a single intravenous dose of 1.8 mg/kg is the optimum single intravenous dose for controlling chemotherapy-induced emesis in pediatric patients.

Adolescent↗
PubMed1999

Neuropsychologic deficits in children with Langerhans cell histiocytosis.

BACKGROUND: Manifestations of Langerhans cell histiocytosis (LCH) in children range from only a rash, to bony lesions accompanied by pain, to major organ disease. When the central nervous system (CNS) is affected, the LCH patient may exhibit signs and symptoms of hypothalamic and pituitary dysfunction (most often resulting in diabetes insipidus or other endocrinopathies) or more global neurologic and neuropsychologic sequelae. Surprisingly, researchers have only recently begun to examine the neuropsychologic manifestations of the disease, but early findings suggest that they may, in fact, be significant in a small percentage of children with LCH. PROCEDURE: We evaluated two CNS-positive patients with LCH and long-term intermittent treatments, using extensive neuropsychologic assessments, including intellectual functioning, memory, visual-motor functioning, attention and concentration, sensory and motor performance, and gross academic achievement. Objective measures of behavior were obtained through parental report. Neuroradiologic imaging was obtained concurrently with the neuropsychologic evaluations. RESULTS: The neuropsychologic assessments indicated significant deficits in a number of the measured areas of functioning. Global cognitive deficiencies in full-scale IQ were identified, as were deficits in memory, attention/concentration, and perceptual-organizational capabilities. Similarities were noted in the patterns of deficits obtained with both patients, despite differences in the pathophysiology of their disease. Behavioral functioning in both children had suffered, presumably in relation to the neuropsychologic deficits. There were radiologic findings of gross cerebellar white matter damage in one patient, in addition to focal (e.g., hypothalamic) lesions in the other. CONCLUSIONS: LCH has an adverse impact on cognitive functions in some children with evidence of CNS involvement, and further study into the etiology, incidence, and means of remedial intervention is needed.

Adolescent↗
PubMed1999

Allogeneic blood stem cell and bone marrow transplantation for acute myelogenous leukemia and myelodysplasia: influence of stem cell source on outcome.

We have compared the outcomes of 87 patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) receiving matched sibling transplants with stem cells from peripheral blood (blood cell transplant, BCT) or bone marrow (BMT). In good risk patients (AML in CR1) granulocytes recovered to 0.5 x 10(9)/l a median of 14 days after BCT compared with 19 days after BMT (P < 0.0001). For patients with poor risk disease (AML beyond CR1 and MDS) corresponding figures were 16 vs 26 days (P < 0.0001). Platelet recovery to 20 x 10(9)/l was also faster after BCT (good risk 12 vs 20 days, P < 0.0001; poor risk 17 vs 22 days, P = 0.04). Red cell transfusions were unaffected by cell source, but BCT recipients required less platelet transfusions (good risk 1 vs 5, P = 0.002; poor risk 5 vs 11, P = 0.004). Blood cell transplants resulted in more chronic GVHD (86% vs 48%, P = 0.005) and a significantly higher proportion of recipients with KPS of 80% or less (48% vs 5%, P = 0.004). Disease-free survival at 4 years was 23% for both groups of poor risk patients but outcome in good risk patients was better after BCT (93% vs 62%, P = 0.047) related mainly to less relapse. While disease-free survival may be better after BCT than BMT for AML in CR1, quality of life may be relatively impaired.

Adolescent↗
PubMed1999

Genetics of Wilms' tumor.

The molecular genetic characterization of Wilms' tumor has played a prominent role in advancing our knowledge of the genetic aspects underlying the development of cancer in general. Unlike the genetic mechanism leading to the development of retinoblastoma, an embryonal tumor of childhood affecting the retina, which only requires the inactivation of one single gene, the biological pathways leading to the development of Wilms' tumor are complex and likely involve several genetic loci. These include two genes on chromosome 11p; one on chromosome 11p13 (the Wilms' tumor suppressor gene WT1) and the other on chromosome 11p15 (the putative Wilms' tumor suppressor gene WT2). In addition to these two genes, loci at 1p, 7p, 16q, 17p (the p53 tumor suppressor gene), and 19q (the putative familial Wilms' tumor gene FWT2) are also believed to harbor genes involved in the biology of Wilms' tumor. Herein these loci are reviewed and their clinical significance is summarized.

Genes, Wilms Tumor↗
PubMed1999

Long-term complications and post-treatment follow-up of patients with Wilms' tumor.

An increasing number of children with Wilms' tumor can expect to be cured, reflecting the undisputed progress made in the treatment of children with this renal cancer. However, it does underscore the need to screen survivors for late effects of cancer therapy. Some of the late effects, such as those following radiation therapy, should be expected after a considerable latent period. Others, such as those occurring after the administration of certain chemotherapeutics agents, are commonly immediate, usually transient, but occasionally permanent. Although children seem to tolerate acute toxicities of therapy better than do adults, the growing child may be more vulnerable to the delayed adverse sequelae of cancer therapy, such as effects on growth, fertility, and neuropsychological function. This article reviews many of the late effects seen in survivors of Wilms' tumor and the way in which these effects relate to the different therapeutical modalities used (surgery, chemotherapy, and radiation).

Antineoplastic Agents↗
PubMed1998

Current concepts in the biology and management of Wilms tumor.

PURPOSE: There have been a number of advances that have increased our understanding of the biology of Wilms tumor during the last decade. This information is now being incorporated into current pediatric oncology protocols. We present a summary of these advances and outline the current treatment of Wilms tumor. MATERIALS AND METHODS: The medical literature was reviewed with an emphasis on the molecular biology of Wilms tumor. RESULTS: The development of Wilms tumor involves several genes, including WT1, the Wilms tumor suppressor gene at 11p13. In addition, certain chromosomal regions (16q and 1p) might be used as prognostic factors for determining the intensity of therapy. CONCLUSIONS: Future protocols conducted by pediatric oncology groups will incorporate biological studies. The goal is to identify patients at low risk for relapse which will allow a reduction in treatment intensity and subsequent toxicity. Children at an increased risk for relapse can be selected for more intensive treatment.

Child↗
PubMed1997

Cutaneous toxicity following the administration of dactinomycin.

Dactinomycin (AMD) is an effective drug in the management of several malignant disorders and has been used for almost 40 years. Skin and subcutaneous toxicities following extravasation are well known and can be harmful. Similarly radiation-recall is a well established phenomenon following the administration of AMD. We report a patient who developed a localized brawny erythema in the crural folds and the axillae, likely due to AMD. This rare skin complication of AMD seems to benefit from topical corticosteroid treatment, although postinflammatory hyperpigmentation may take months to disappear.

Administration, Cutaneous↗
PubMed1997

Fractionated cylophosphamide and back to back high dose methotrexate and cytosine arabinoside improves outcome in patients with stage III high grade small non-cleaved cell lymphomas (SNCCL): a randomized trial of the Pediatric Oncology Group.

BACKGROUND: The Pediatric Oncology Group (POG) conducted a two-arm, randomized study for the treatment of children and adolescents with stage III small, non-cleaved cell lymphoma (SNCCL). Regimen A, based on the group's previous best treatment for this group of patients, included cyclophosphamide (CTX) and high-dose methotrexate (MTX), as well as vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemoprophylaxis. Regimen B, based on a single institution pilot study (Total B therapy), consisted of two rapidly alternating chemotherapy combinations (CTX, VCR, doxorubicin; MTX, and cytarabine (Ara-C) plus coordinated IT chemotherapy. PROCEDURE: One hundred thirty-four consecutive patients were entered on this study. Seventy patients were randomized to Regimen A, and 64 patients to Regimen B. One hundred and twenty-two patients are eligible for response. RESULTS: Complete remission (CR) was achieved by 81% (52/64) of patients on Regimen A, and 95% (55/58) of patients on Regimen B (p=0.014 one-sided). The two-year event-free survival (EFS) is 64% (SE=6%) on Regimen A, and 79% (SE=6%) on Regimen B (p=0.027 by one-sided logrank test). No patient has relapsed on either regimen after a year from diagnosis, although one patient had a second malignancy at day 371. Severe, but manageable, hematologic toxicity was seen in the majority of patients on both regimens, but was more frequent on Regimen B. CONCLUSIONS: We conclude that the cure rate in stage III SNCCL is significantly improved with the use of a short, six-month chemotherapy regimen of fractionated CTX alternated with coordinated MTX and Ara-C. Results suggest that drug schedule, not simple drug selection, influences outcome.

Adolescent↗