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At least 343 records · Page 19Linked to original sources
PubMed2006

DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes.

Human cancers exhibit genomic instability and an increased mutation rate due to underlying defects in DNA repair. Cancer cells are often defective in one of six major DNA repair pathways, namely: mismatch repair, base excision repair, nucleotide excision repair, homologous recombination, nonhomologous endjoining and translesion synthesis. The specific DNA repair pathway affected is predictive of the kinds of mutations, the tumor drug sensitivity, and the treatment outcome. The study of rare inherited DNA repair disorders, such as Fanconi anemia, has yielded new insights to drug sensitivity and treatment of sporadic cancers, such as breast or ovarian epithelial tumors, in the general population. The Fanconi anemia pathway is an example of how DNA repair pathways can be deregulated in cancer cells and how biomarkers of the integrity of these pathways could be useful as a guide to cancer management and may be used in the development of novel therapeutic agents.

Adolescent↗
PubMed1993

Management of indwelling central venous catheters in pediatric cancer patients with fever and neutropenia.

This prospective study comprises 97 episodes of fever and neutropenia in children with cancer and central venous access. In 76% of episodes, patients had a Broviac-Hickman-like catheter, and in 24% a totally implanted venous access chamber system. The need for catheter removal during a febrile infection was 0.32/1000 catheter days, and the documented sepsis rate was 0.59/1000 catheter days. Our data indicate that 94% of episodes of fever and neutropenia in total, 78% of documented septicemias, and 97% of fevers of unknown origin were curable with broad-coverage antimicrobial therapy without removing the central venous line. Totally implanted chambers had a lower infection rate than catheters of Broviac-Hickman type.

Adolescent↗
PubMedDate not supplied

Pharmacokinetic analysis of vancomycin in steady state in pediatric cancer patients.

Thirty children suffering from different types of malignancies, neutropenic fever, and suspected staphylococcal bacteremia were evaluated for the pharmacokinetics of vancomycin in steady-state conditions and compared with eight children suffering from proven methicillin-resistant staphylococcal infection. All the studied population received intravenous vancomycin at 40 mg/kg daily divided into four daily doses. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood vancomycin samples. The mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax (microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours; 0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8) and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the malignancy and control groups, respectively. The malignancy group had a significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower Cmin (P = .03) in comparison with the control group. It is suggested that the prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is safe and will provide a peak blood level of vancomycin sufficient to cover the broad spectrum of staphylococcal bacteria. The vancomycin dose should be individualized, based on an individual pharmacokinetic profile.

Anti-Bacterial Agents↗
PubMed2001

[Changes of the incidence and survival in pediatric malignant tumors between 1988-1997, according to the data of the Hungarian Pediatric Cancer Registry].

This paper reports the results of the epidemiological surveillance of childhood malignancies in Hungary from 1988 through 1997, according to the database of the Hungarian Paediatric Cancer Registry. The number of analysed cases was 2146. The crude incidence of all childhood malignancies was 132 per one million person-years. The number of new cases diagnosed in Hungary varied between 240 to 280 per year. This number did not change significantly over the observed period in spite of the decreasing number of children in Hungary, therefore, the incidence showed a significant increase of 3.3% per year. The authors also present data about the geographical distribution of childhood cancer in Hungary and survival rates for different tumour types. The 10-year overall survival rate of all malignant diseases diagnosed in Hungary during the analysed ten-year period was 62.6%.

Adolescent↗
PubMed2004

Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

Adolescent↗
PubMed1990

[Peripheral blood stem cell autografts in pediatric cancer].

Harvest of peripheral blood stem cells (PBSC) for autografts is a safe, reliable procedure with low morbidity in children with cancer, and cryopreserved PBSC are useful in reducing cytopenia following marrow-ablative chemotherapy. The colony forming unit granulocyte/macrophage (CFU-GM) content of the thawed grafts is an important determinant of hematopoietic recovery after PBSC autografts. The possible value of high-dose chemotherapy without total body irradiation and PBSCT compared to intensified chemotherapy in the treatment of children with very high-risk lymphoid malignant disorders was reported.

Adolescent↗
PubMed1990

Pharmacokinetics of continuous infusion of methotrexate and teniposide in pediatric cancer patients.

Laboratory studies have demonstrated the ability of teniposide to markedly enhance the intracellular accumulation of methotrexate suggesting that combination therapy with these agents may produce clinical benefit. Studies of methotrexate and teniposide were conducted in 19 children with relapsed acute lymphocytic leukemia to evaluate the pharmacokinetics of this previously untested combination of agents given alone or in combination and to demonstrate the feasibility of a Bayesian dose optimization strategy. Patients were randomly assigned to receive intermediate dose methotrexate as a 24-h continuous infusion, administered either simultaneously with continuous infusion teniposide or sequentially with the teniposide infusion beginning 12 h after the end of the methotrexate infusion. Plasma samples were obtained during and after infusions at appropriate times for a comprehensive pharmacokinetic study of each drug. Two measured drug concentrations obtained during the infusion were used to adjust each patient's dose rate to achieve target values of 10 microM for methotrexate and 15 microM for teniposide. Pharmacokinetic parameters for teniposide were not different for patients given simultaneous methotrexate from parameters estimated for patients receiving teniposide 12 h after the end of the methotrexate infusion. Despite similar end of infusion methotrexate concentrations, 24-h postinfusion methotrexate concentrations were lower (0.137 versus 0.235 microM; P less than 0.05) in the patients receiving simultaneous infusions. The patient specific dose regimens yielded acceptably precise, minimally biased steady state drug concentrations. These pharmacokinetic results provide the basis for further clinical studies with this combination of antileukemic agents.

Antineoplastic Combined Chemotherapy Protocols↗