https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54339 Wed 28 Feb 2024 15:10:12 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22785 Wed 11 Apr 2018 16:59:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39890 Thu 14 Jul 2022 14:21:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29998 –2) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (≥ grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression-free survival and overall survival (OS). Results: Melphalan AUC ranged from 4.9 to 24.6 mg l^–1 h, median 12.84 mg l–1 h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P = 0.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P = 0.001), with an estimated median survival of 8.50 years vs. 5.38 years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression-free survival. Conclusions: This large scale pharmacodynamic analysis of HDM demonstrates that high melphalan exposure is associated with improved survival, with an acceptable increase in transplant toxicity. These results suggest studies targeting a higher AUC are warranted in patients undergoing HDM and ASCT for myeloma.]]> Thu 13 Jan 2022 10:31:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:989 Sat 24 Mar 2018 08:29:49 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10455 Sat 24 Mar 2018 08:09:17 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20771 vs as-needed 1·05, 0·92–1·20). We recorded no difference between treatment groups for time to recovery (adjusted p=0·79). Adherence to regular tablets (median tablets consumed per participant per day of maximum 6; 4·0 [IQR 1·6–5·7] in the regular group, 3·9 [1·5–5·6] in the as-needed group, and 4·0 [1·5–5·7] in the placebo group), and number of participants reporting adverse events (99 [18·5%] in the regular group, 99 [18·7%] in the as-needed group, and 98 [18·5%] in the placebo group) were similar between groups. Interpretation: Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group.]]> Sat 24 Mar 2018 08:00:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:46640 Mon 28 Nov 2022 16:47:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53882 0.872; correlation coefficient, r = 0.87, P < 0.0001). Conclusions: DBS provides an alternative sampling strategy for the TDM of many anticancer drugs. Further research is required to establish a standardized approach for sampling and processing DBS samples to allow future implementation.]]> Fri 19 Jan 2024 14:22:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:55344 Fri 17 May 2024 15:50:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40009 n = 61) were analysed using non-linear mixed modelling. Covariate analysis was performed to investigate the impact of standard and novel patient characteristics of carboplatin pharmacokinetics. A Monte Carlo simulation of 100,000 representative NSCLC patients evaluated the ability of the Calvert formula and novel dosing strategies to achieve the targeted therapeutic range. The associations between systemic inflammation and chemotherapy drug utilisation (cycles received, relative dose intensity (RDI) and second-line uptake) and clinical endpoints were also investigated in the pharmacokinetic cohort, and two independent cohorts of people with advanced NSCLC from the Chemotherapy Dosing in Cancer-Related Inflammation (CDCRI) database that were administered carboplatin–paclitaxel (n  = 37) or carboplatin–gemcitabine (n  = 358). Results: In all cohorts, 25–53% of people had elevated systemic inflammation (NLR > 5 or PLR > 300). In the pharmacokinetic cohort, no patients achieved the desired therapeutic target of carboplatin. Carboplatin exposure was related to renal function, as estimated using the Cockcroft–Gault formula, albumin and inflammation (NLR). In the pharmacokinetic cohort, increasing carboplatin area under the curve (AUC) correlated with greater reductions in red blood cells and haemoglobin. In this cohort, the average measured AUC of partial responders was 2.4 mg·min/mL. Also in the pharmacokinetic cohort, only 12% of people with an NLR > 5 received four or more cycles of chemotherapy, compared with 62% of patients with an NLR ≤ 5 (p < 0.001). For people in the CDCRI cohort receiving carboplatin–gemcitabine, those with an NLR > 5 also received less cycles (four or more cycles, 41% vs. 60%; p < 0.01) as well as less second-line chemotherapy (46% vs. 60%; p = 0.02) compared with patients without inflammation. People in the pharmacokinetic cohort with an NLR > 5 had 12 months less median survival compared with people with an NLR ≤ 5 (6.5 vs. 18 months; p = 0.08). Similarly, overall survival was significantly shortened in people in the CDCRI cohort receiving carboplatin–gemcitabine with an NLR > 5 compared with those with an NLR ≤ 5 (7 vs. 12 months; p < 0.001), and Cox regression analysis showed a 1.5-fold (1.3–2.1; p < 0.001) increased hazard of death associated with the increased systemic inflammation. Simulations of the newly developed model-based and Calvert dosing assessed the ability to reach this study’s proposed actual target AUC of 2.2–2.6 mg·min/mL. These showed current Calvert dosing was predicted to result in substantial overexposure in patients with high systemic inflammation. The newly developed model showed equivalent levels of carboplatin therapeutic target achievement across the spectrum of inflammation observed in the lung cancer population. Conclusion: An alternate model-based dosing strategy for carboplatin was developed and is predicted to result in consistent drug exposure across the population and improve attainment of therapeutic targets. Further studies of this new model are warranted in people with advanced NSCLC.]]> Fri 15 Jul 2022 11:35:17 AEST ]]>