PubMed · 10969615
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L Dogliotti, C Garufi, S Iacobelli. [Chronochemotherapy].. https://doi.org/10.1177/03008916000863s111
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Cytosine arabinoside (ara-C) and 2',2'-difluorodeoxycytidine (Gem) were compared in leukemia cells, with Gem being more potent than ara-C. Gem was combined with hexadecylphosphocholine (HPC) or erucylphospho-N,N,N-trimethylpropanolamine (ErPC(3)) in resistant CML cells. Supra-additive effects were seen in K-562 cells after concomitant and sequential exposure of Gem followed by HPC. The reverse sequence resulted in antagonism. Both effects were more significant when HPC was exchanged for ErPC(3). Gem or HPC failed to induce DNA laddering in K-562 cells, but apoptotic signals were transferred by the Gem-exposed SKW-3 cytosolic fraction to K-562 nuclei. HPC did not increase the clastogenicity of Gem and counteracted its mitotic inhibition in murine bone marrow. Thus, the combination of Gem and an alkylphosphocholine is advantageous in terms of their complementary mode of action, resulting in increased cytotoxicity and lowered myelotoxicity.
A kinetic study of the oxidation of methotrexate (MTX) in acidic medium and in the presence of potassium permanganate has been made on the basis of the fluorescence-time curves. A kinetic method for the determination of MTX was developed with a range of application between 0.22 and 3.30 microM. The proposed kinetic method permits us to determine MTX in human serum and to avoid the natural fluorescence of the serum. A detection limit of 0.18 microM was calculated in the presence of ascorbic acid as activator. Only 100 s per sample is necessary for the analysis. The interference of pteridin derivatives and the rescue agent folinic acid (leucovorin) was tested.
Many different statistical designs have been used in phase II clinical trials. The majority of these are based on frequentist statistical approaches. Bayesian methods provide a good alternative to frequentist approaches as they allow for the incorporation of relevant prior information and the presentation of the trial results in a manner which, some feel, is more intuitive and helpful. In this paper, we propose two new Bayesian designs for phase II clinical trials. These designs have been developed specifically to make them as user friendly and as familiar as possible to those who have had experience working with two-stage frequentist phase II designs. Thus, unlike many of the Bayesian designs already proposed in the literature, our designs do not require a distribution for the response rate of the currently used drug or the explicit specification of utility or loss functions. We study the properties of our designs and compare them with the Simon two-stage optimal and minimax designs. We also apply them to an example of two recently concluded phase II trials conducted at the National Cancer Centre in Singapore. Sample size tables for the designs are given.