Alan Boddy

..To determine the safety, maximum tolerated dose, pharmacokinetics, and toxicities associated with administration of paclitaxel poliglumex (PPX, XYOTAX, Cell Therapeutics, Inc., Bresso, Italy) given on either 3-weekly or 2-weekly schedule...

..Further advances in analytical and molecular pharmacological techniques may further optimise their use and allow rational design of more selective analogues...

..To investigate the potential use of accelerator mass spectrometry (AMS) in the study of the clinical pharmacology of imatinib...

..To determine the effect on systemic pharmacology and clinical toxicity of dose and mode of administration of paclitaxel combined with carboplatin in the treatment of ovarian cancer...

..Intrinsic differences between the two complexes, primarily reactivity, probably explain the lower adduct levels observed after carboplatin treatment...

..The response of neuroblastoma cells to R116010 was consistent with inhibition of CYP26, indicating that inhibition of RA metabolism may further optimise retinoid treatment in neuroblastoma...

..Pharmacodynamic data suggest a strong correlation between carboplatin pharmacokinetics and the drug-target interaction...

..These data suggest considerable potential for CYP26 inhibitors in the future treatment of neuroblastoma with 13cisRA...

..These results imply that analysis of adducts in PBLs after incubation of pretreatment blood samples with cisplatin may be used to predict in vivo adduct levels, leukopenia, and, potentially, response to cisplatin therapy...

..A standard methodology for estimating GFR should be followed to achieve uniform dosing in children with cancer...

..The results of this study, with only a small number of patients, need to be confirmed in future investigations...

..The article reports safety, efficacy, pharmacokinetic, and pharmacodynamic results of the first-in-class trial of a PARP inhibitor, AG014699, combined with temozolomide in adults with advanced malignancy...

..One patient remains alive and symptom-free at 4 years after treatment. Temozolomide and paclitaxel may be administered safely at clinically effective doses. Further evaluation of these combinations in melanoma is warranted...

..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...

..For all three drugs, interoccasion variability was of the same order (20-40%) as that between individuals, suggesting a limited potential for dose-optimisation of this regimen...

..Studies in vitro suggest some synergy, however, due to a pharmacokinetic interaction, paclitaxel doses should be reduced when administered during nolatrexed infusion...

..The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin...

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..It is not known whether this genetic variation has an impact on the efficacy or toxicity of AC therapy...

..Fractionated dosing causes a greater degree of DNA damage, which may suggest a greater degree of efficacy, with a good correlation between pharmacokinetic and pharmacodynamic data...

..d. 4.67+/-3.17 microM) higher than those of 13-cisRA (2.83+/-1.44 microM) in 16 out of 23 patients on day 14 of course 2. Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of 13-cisRA...

..7 and 20.0%. These simple additive models provide a more rationale approach than the use of complex formulae, involving additional parameters, to predict renal function...

..05 to 0.2 micromol/L (t(C > 0.05-0.2)) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients...

..In summary, these results indicate either an intracellular conversion of 13-cis RA to ATRA or a selective uptake of ATRA and suggest that this may mediate the differential activity of 13-cis RA in neuroblastoma cell subtypes...

..Relationships between pharmacokinetics and toxicity will be examined in future prospective studies in which children less than 1 year old will be enrolled...

..CONCLUSIONS: The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be significant...

..The NQO activity of ovarian and bladder tumors was determined and the effect of NQO polymorphisms on NQO activity was investigated...

..8%, respectively. Accuracy data showed relative errors of 2.0-16.4 and 10.4-15.2% for intra-assay (n=10) and inter-assay (n=7) experiments, respectively. Initial results of actinomycin D pharmacokinetics in paediatric patients are shown...

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..The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor...

..CONCLUSIONS: Data presented suggest that dosing of dactinomycin based on surface area is not optimal, either in younger patients in whom the risk of toxicity is greater, or in older patients where doses are capped...

..We assessed toxicities and explored the activity of the drug combination exclusively in patients with malignant pleural mesothelioma (MPM). The pharmacokinetics of both agents was investigated...

..Research involving children with cancer should be limited to those studies addressing key scientific questions and should be designed to limit both the number and volume of blood samples required...

..2-[11C]Thymidine PET can be used to measure thymidine salvage kinetics directly in the tissue of interest...

..These unusual cases provided an opportunity to investigate the biliary clearance of etoposide by determining etoposide concentrations in bile and plasma samples obtained during chemotherapy...

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..Modified chemotherapy strategies should be considered in patients who exhibit low rates of clearance of the parent drug and/or extensive production of inactive metabolites...

..Extending the use of these approaches to pharmacodynamic end-points, together with the application of population-based modelling techniques, offers the potential to develop truly individualized therapy in the future...