Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 27 for “"maximum tolerated dose"”.
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The Effects of Metronomic and Maximum-Tolerated Dose Chemotherapy in Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy and mRNA Expression
… associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for …
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Sustained-release implants for intraperitoneal cisplatin delivery
… work was to develop materials for continuous low-dose delivery of cisplatin directly into the abdomen, also known as intraperitoneal (IP) chemotherapy. IP chemotherapy can help treat peritoneal metastasis in many advanced gynecologic and gastrointestinal cancers and has shown particular promise in …
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A Phase I Dose-Escalation Study of The Braf Inhibitor Vemurafenib In Combination With The Mtor Inhibitor Everolimus In Subjects With Advanced Cancer
… of vemurafenib and everolimus will be well tolerated. The primary objective is to find the maximum tolerated dose (MTD) and the toxicity of the combination of vemurafenib and everolimus following a standard 3 + 3 design. The most common diagnosis was melanoma in 5 out of 10 patients (50%). …
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Modified 3+3 Design for MTD Re-estimation
… clinical trial design is one of the most popular dose-finding designs used in phase I oncology trials to identify the maximum tolerated dose (MTD) for new treatment regimens. While this design is widely used due to its simplicity , it has some notable limitations, including a maximum of six …
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Dual-Criterion Dose Finding Designs for Phase I Clinical Trials
… tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many …
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Therapeutic Effects and Targeted Delivery of Eupenifeldin in Castration-Resistant Prostate Cancer
… Eupenifeldin inhibits cell proliferation in a dose-dependent manner and induces apoptotic cell death through caspase-3/7 activation, suggesting that apoptotic pathways mediate its anticancer effects. Mechanistic studies revealed that Eupenifeldin caused a broad reduction in kinase …
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Development and Evaluation of Organometallic Anticancer Drug Candidates
… series of assays including determination of the maximum tolerated dose and pharmacodynamic studies. Structural modifications of the lead molecule with water-soluble phosphines were subsequently undertaken, with the aim to improve the stability and solubility of the parent 16-electron specie, and …
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Development and Evaluation of Organometallic Anticancer Drug Candidates
… series of assays including determination of the maximum tolerated dose and pharmacodynamic studies. Structural modifications of the lead molecule with water-soluble phosphines were subsequently undertaken, with the aim to improve the stability and solubility of the parent 16-electron specie, and …
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Novel Phase I/II Designs for Cytotoxic and Cytostatic Agents, and Combination Treatments
… develops innovative Bayesian adaptive dose-finding designs for early-phase oncology trials, aiming to improve the identification of optimal biological doses (OBDs) by jointly modeling safety and efficacy. Unlike conventional Phase I designs that rely solely on binary toxicity outcomes …
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Bayesian Adaptive Clinical Trial Design
… and dysfunctional. Specifically, the focus of dose-finding trials has shifted from finding the maximum tolerated dose (MTD) to the optimal biological dose (OBD), defined as the dose that optimizes the risk–benefit tradeoff. How to accurately identify the OBD and its dosing schedule is of great …
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Advancing the Preclinical Development of Secondary Metabolites from Cacospongia mycofijiensis for the Treatment of Cancer
… mechanism of action studies, and determining the maximum tolerated dose in mice. Data gathered from these preclinical studies showed the notable potency both in vitro against cancer cell lines and when evaluated using in vivo models, as well as provided important data on the SAR of compounds …
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Approaches to the assembly of potent therapeutic agents for the treatment of myotonic dystrophy
… Drosophila model. However, its relatively low maximum tolerated dose in mice and limited cell uptake provide insights into directions for future development. In addition, a powerful selection method that uses the target DNA or RNA to select their own binders will be discussed in Chapter 4. …
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Bayesian Phase I Dose Finding In Cancer Trials
<p>This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model.</p> <p>We list …
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Renal and Blood Pressure Effects of Xanthine Oxidase Inhibitors in the FAST trial
… >357 µmol/L require up-titration of allopurinol dose to achieve EULAR recommended sUA levels prior to randomisation. The up-titration process involves increasing allopurinol dose by 100mg and re-checking sUA after 2 weeks. Dose increases of 100mg are repeated every fortnight until sUA is <357 …
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The development of deoxynyboquinone as a personalized anticancer compound
… DNQ must be delivered at concentrations near the maximum tolerated dose in mice to achieve maximal efficacy. In addition, the poor aqueous solubility of DNQ necessitated the use of a formulation containing a high concentration of 2-hydroxypropyl-b-cyclodextrin (HPbCD) which would complicate …
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Evaluation of the Pharmacokinetic-Pharmacodynamic relationship, Metabolism and Plasma Protein Binding of the novel antitumor agent, 2-Methoxyestradiol (2ME2), following oral administration in patients with solid tumors.
… 2ME2 in patients with solid tumors and determine maximum tolerated dose (MTD). The following hypotheses were tested: 1) 2ME2 will be well tolerated in clinic when given orally and will have quantifiable effects on the ex vivo markers of angiogenesis and apoptosis; 2) 2ME2 will exhibit linear …
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Drug delivery of paclitaxel for an intraperitoneal chemotherapy
… the toxicity of both formulations was similar (maximum tolerated dose (MTD) of 0.24 mg/ml for both). Bioavailability, however, was significantly increased for Pac/RAME-beta-CD (i.e. 40-fold increase for the area under the curve). Preliminary results from the TGD study allowed to establish the …
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Pharmacological characterisation of selected pyrrolobenzodiazepines as anti-cancer agents. Pharmacokinetic and pharmacodynamic characterisation of the pyrrolobenzodiazepine dimer SJG-136 and the monomers D709119, MMY-SJG and SJG-303
… in mice via both the i.p. and i.v. route (dosed at the maximum tolerated dose (MTD)) showed that SJG-136 reaches concentrations in plasma well in excess of the in vitro IC50 values for 1 h exposure, and was detected in tumour and brain samples also above the in vitro IC50 values. …
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Targeting head and neck squamous cell carcinoma through NQO1-mediated cytotoxicity
… in attempts to find a derivative with a greater maximum tolerated dose (MTD) or more favorable pharmacokinetics. Future studies involving NQO1-independent ROS generation, methemoglobin formations and tumor penetrations are currently being investigated to differentiate DNQ derivatives and identify …
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Bayesian Semi-Mechanistic Dose-Finding Designs For Phase I Oncology Trials
… In oncology, despite the great advances in novel dose-finding designs, the high failure rates of clinical cancer drug development from phase I to III trials call for further improvements on novel designs, in addition to the need to promote and adopt novel designs in practice. Because anticancer …
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