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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- van Doorn, Leni, et al.
(författare)
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Effect of Scalp Cooling on the Pharmacokinetics of Paclitaxel
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:15
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary This study investigated the correlation between scalp cooling used to prevent chemotherapy-induced alopecia and the pharmacokinetics of paclitaxel in female cancer patients with a solid tumor. In a prospective cohort study, 14 patients who were treated with weekly paclitaxel and scalp cooling were able to undergo pharmacokinetic sampling of paclitaxel during one cycle of treatment. In comparison to a control cohort of 24 patients treated with weekly paclitaxel without scalp cooling, our data showed that scalp cooling used concomitantly with one course of paclitaxel did not reduce or increase the clearance of paclitaxel. Therefore, it is unlikely that scalp cooling influences paclitaxel efficacy or toxicity. Finally, despite scalp cooling, half of the patients in our study developed a form of hair loss. Importantly, neither an association with difference in paclitaxel clearance nor change in hair loss was found. Chemotherapy-induced alopecia (CIA), a side effect with high impact, can be prevented by cooling the scalp during the administration of some cytotoxic drugs. However, the effects of this prolonged scalp cooling on the pharmacokinetics of chemotherapy have never been investigated. In this study, we compared the pharmacokinetics of the widely used chemotherapeutic agent paclitaxel (weekly dose of 80-100 mg/m(2)) in female patients with solid tumors using concomitant scalp cooling (n = 14) or not (n = 24). Blood samples were collected in all patients for pharmacokinetic analyses up to 6 h after one course of paclitaxel administration. The primary endpoint was the clearance (L/h) of paclitaxel. Paclitaxel clearance-expressed as relative difference in geometric means-was 6.8% (90% CI: -16.7% to 4.4%) lower when paclitaxel was administered with concomitant scalp cooling versus paclitaxel infusions without scalp cooling. Within the subgroup of patients using scalp cooling, paclitaxel clearance was not statistically significantly different between patients with CIA (alopecia grade 1 or 2) and those without CIA. Hence, scalp cooling did not negatively influence the clearance of paclitaxel treatment.
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| 5. |
- Toxopeus, Eelke L. A., et al.
(författare)
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Association between Paclitaxel Clearance and Tumor Response in Patients with Esophageal Cancer
- 2019
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Inter-individual variability in paclitaxel pharmacokinetics may play a role in the response to chemotherapy. Therefore, we studied the association between paclitaxel clearance and treatment response in patients with esophageal cancer. All patients who received paclitaxel (plus carboplatin) treatment for esophageal cancer between 2007 and 2013 were included. The treatment was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative chemotherapy (pCT). The treatment response was assessed by the tumor regression grade (TRG) or by the RECIST1.1 criteria, respectively. The unbound paclitaxel clearance (CL) was estimated with NONMEM. The log-transformed clearance was related to response with ANOVA and independent sample t-tests. A total of 166 patients were included, of whom 113 received nCRT, 23 iCT and 30 pCT. In patients receiving nCRT, paclitaxel clearance was not associated with tumor regression grade (p-value = 0.25), nor with pathologically complete response (geometric mean 561.6 L/h) and residual disease (geometric mean 566.1 L/h, p-value = 0.90). In patients who underwent iCT or pCT, also no association between paclitaxel clearance and RECIST outcome was identified (iCT: p-value = 0.08 and pCT: p-value = 0.81, respectively). In conclusion, systemic paclitaxel exposure was not associated with response to common paclitaxel-based treatment regimens for esophageal cancer. Future studies should focus on tumor exposure in relation to systemic exposure and treatment outcome.
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| 6. |
- van Eerden, Ruben A. G., et al.
(författare)
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Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer
- 2021
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media S.A.. - 1663-9812. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression and intratumoral pharmacokinetics of paclitaxel to identify changes which could be a first sign of chemoresistance.Methods: Patients with esophageal cancer treated with paclitaxel and carboplatin (+/- concomitant radiotherapy) were included. During the first and last cycle of weekly paclitaxel, blood samples and biopsies of esophageal mucosa and tumor tissue were taken. Changes in paclitaxel exposure and expression of ABCB1 (P-glycoprotein) over time were studied in both tumor tissue and normal appearing esophageal mucosa.Results: ABCB1 was significantly higher expressed in tumor tissue compared to esophageal tissue, during both the first and last cycle of paclitaxel (cycle 1: p < 0.01; cycle 5/6: p = 0.01). Interestingly, ABCB1 expression was significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.01). During the first cycle, a trend towards a higher intratumoral paclitaxel concentration was observed compared to the esophageal mucosa concentration (RD:43%; 95%CI: -3% to 111% p = 0.07). Intratumoral and plasma paclitaxel concentrations were significantly correlated during the first cycle (AUC(0-48 h): r = 0.72; p < 0.01).Conclusion: Higher ABCB1 expression in tumor tissue, and differences between histological tumor types might partly explain why tumors respond differently to systemic treatment. Resistance by altered intratumoral paclitaxel concentrations could not be demonstrated because the majority of the biopsies taken at the last cycle of paclitaxel did contain a low amount of tumor cells or no tumor.
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| 7. |
- de Rie, MA, et al.
(författare)
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Pharmacoeconomic evaluation of calcipotriol (Daivonex/Dovonex) and UVB phototherapy in the treatment of psoriasis: a Markov model for The Netherlands
- 2001
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Ingår i: Dermatology (Basel, Switzerland). - : S. Karger AG. - 1018-8665 .- 1421-9832. ; 202:1, s. 38-43
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The high prevalence and chronic nature of psoriasis leads to high costs in relation to the treatment and control of the disease. A number of clinical trials have shown that a combination therapy of calcipotriol cream (Daivonex<sup>®</sup>/Dovonex<sup>®</sup>, Leo Pharmaceutical Products) and ultraviolet B phototherapy (UVB) decreases the total number of UVB exposures required compared to UVB treatment alone. From a societal point of view, the addition of calcipotriol to UVB therapy could achieve cost savings due to the fewer UVB treatments needed and the reduced travelling and time off work for patients. Fewer UVB exposures may also have other beneficial effects, i.e., shortened waiting lists and less risk to patients of developing cancer or photoaging of the skin. <i>Objective:</i> To compare the cost-effectiveness of treating psoriatic patients in the Netherlands with calcipotriol cream used daily combined with twice weekly UVB treatments to emollient used daily combined with UVB given 3 times weekly. <i>Methods:</i> Based on the clinical results from a Canadian trial, a decision-analytical model was constructed to simulate treatment outcomes and estimate the costs of managing psoriatic patients in the Netherlands over a period of 20 weeks from initiation of therapy. Unit costs and details of standard treatment protocols were collected from Dutch dermatology centres in hospitals and the community for use in the model. Other therapies, such as topical corticosteroids, tar or dithranol were not investigated in this analysis. <i>Results:</i> The total cost of managing psoriatic patients in the Netherlands over a 20-week period is estimated as EUR 1,175.90 for those treated with calcipotriol and UVB and EUR 1,212.14 for patients treated with emollient and UVB. Thus, the former treatment, adding calcipotriol to UVB phototherapy, provides a minor cost saving of EUR 36.24 (3%) compared to the cost of UVB treatment alone. Sensitivity analyses demonstrated that these results are sensitive to changes in the cost of UVB treatment. <i>Conclusion:</i> Calcipotriol treatment combined with UVB phototherapy is a cost-neutral alternative to UVB phototherapy used with an emollient. The patients achieve treatment success in the same time on both treatments but the former, with calcipotriol, requires less exposure to UVB radiation. The additional drug costs from using calcipotriol are offset by savings from the fewer UVB sessions required. Essential beneficial effects for patients are less inconvenience, less risk of developing photoaging of the skin and less exposure to potentially carcinogenic radiations.
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| 8. |
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| 9. |
- Jonsson, B. Lars G., et al.
(författare)
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Retrofocusing of acoustic wave fields by iterated time reversal
- 2004
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Ingår i: SIAM Journal on Applied Mathematics. - : Society for Industrial & Applied Mathematics (SIAM). - 0036-1399 .- 1095-712X. ; 64:6, s. 1954-1986
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Tidskriftsartikel (refereegranskat)abstract
- In the present paper an iterative time-reversal algorithm that retrofocuses an acoustic wave field to its controllable part is established. For a fixed temporal support, i.e., transducer excitation time, the algorithm generates an optimal retrofocusing in the least-squares sense. Thus the iterative time-reversal algorithm reduces the temporal support of the excitation from the requirement of negligible remaining energy to the requirement of controllability. The time-reversal retrofocusing is analyzed from a boundary-control perspective where time reversal is used to steer the acoustic wave field towards a desired state. The wave field is controlled by transducers located at subsets of the boundary, i.e., the controllable part of the boundary. The time-reversal cavity and time-reversal mirror cases are analyzed. In the cavity case, the transducers generate a locally plane wave in the fundamental mode through a set of ducts. Numerical examples are given to illustrate the convergence of the iterative time-reversal algorithm. In the mirror case, a homogeneous half space is considered. For this case the analytic expression for the retrofocused wave field is given for finite temporal support. It is shown that the mirror case does not have the same degree of steering as the cavity case. It is also shown that the pressure can be perfectly retrofocused for infinite temporal support. Two examples are given that indicate that the influence of the evanescent part of the wave field is small.
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