| 1. |
- Berglund, Åke, et al.
(author)
-
First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies
- 2015
-
In: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 33:6, s. 1232-1241
-
Journal article (peer-reviewed)abstract
- Purpose Melflufen (melphalan flufenamide, previously designated J1) is an optimized and targeted derivative of melphalan, hydrolyzed by aminopeptidases overexpressed in tumor cells resulting in selective release and trapping of melphalan, and enhanced activity in preclinical models. Methods This was a prospective, single-armed, open-label, first-in-human, dose-finding phase I/IIa study in 45 adult patients with advanced and progressive solid tumors without standard treatment options. Most common tumor types were ovarian carcinoma (n = 20) and non-small-cell lung cancer (NSCLC, n = 11). Results In the dose-escalating phase I part of the study, seven patients were treated with increasing fixed doses of melflufen (25-130 mg) Q3W. In the subsequent phase IIa part, 38 patients received in total 115 cycles of therapy at doses of 30-75 mg. No dose-limiting toxicities (DLTs) were observed at 25 and 50 mg; at higher doses DLTs were reversible neutropenias and thrombocytopenias, particularly evident in heavily pretreated patients, and the recommended phase II dose (RPTD) was set to 50 mg. Response Evaluation Criteria In Solid Tumors (RECIST) evaluation after 3 cycles of therapy (27 patients) showed partial response in one (ovarian cancer), and stable disease in 18 patients. One NSCLC patient received nine cycles of melflufen and progressed after 7 months of therapy. Conclusions In conclusion, melflufen can safely be given to cancer patients, and the toxicity profile was as expected for alkylating agents; RPTD is 50 mg Q3W. Reversible and manageable bone marrow suppression was identified as a DLT. Clinical activity is suggested in ovarian cancer, but modest activity in treatment of refractory NSCLC.
|
|
| 2. |
- Ekman, Simon, et al.
(author)
-
A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma : A phase I clinical trial
- 2016
-
In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:2, s. 140-148
-
Journal article (peer-reviewed)abstract
- BACKGROUND: A phase Ia/b dose-escalation study was performed to characterize the safety, efficacy and pharmacokinetic properties of the oral small molecule insulin-like growth factor-1-receptor pathway modulator AXL1717 in patients with advanced solid tumors.MATERIAL AND METHODS: This was a prospective, single-armed, open label, dose-finding phase Ia/b study with the aim of single day dosing (phase Ia) to define the starting dose for multi-day dosing (phase Ib), and phase Ib to define and confirm recommended phase II dose (RP2D) and if possible maximum tolerated dose (MTD) for repeated dosing.RESULTS AND CONCLUSION: Phase Ia enrolled 16 patients and dose escalations up to 2900 mg BID were successfully performed without any dose limiting toxicity (DLT). A total of 39 patients were treated in phase Ib. AXL1717 was well tolerated with neutropenia as the only dose-related, reversible, DLT. RP2D dose was found to be 390 mg BID for four weeks. Some patients, mainly with NSCLC, demonstrated signs of clinical benefit, including four partial tumor responses (one according to RECIST and three according to PET). The 15 patients with NSCLC with treatment duration longer than two weeks with single agent AXL1717 in third or fourth line of therapy showed a median progression-free survival of 31 weeks and overall survival of 60 weeks. Down-regulation of IGF-1R on granulocytes and increases of free serum levels of IGF-1 were seen in patients treated with AXL1717. AXL1717 had an acceptable safety profile and demonstrated promising efficacy in this heavily pretreated patient cohort, especially in patients with NSCLC. RP2D was concluded to be 390 mg BID for four weeks. Trial number is NCT01062620.
|
|
| 3. |
- Ekman, Simon, et al.
(author)
-
Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor : Experiences in patients with squamous non-small cell lung carcinoma
- 2011
-
In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 50:3, s. 441-447
-
Journal article (peer-reviewed)abstract
- Background. Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. PPP is currently tested as an orally administrated single agent treatment in an open-label combined Phase I/II clinical study in advanced cancer patients with solid tumors which progress in spite of several lines of treatment. Patients and methods. The first part (Phase IA) consisted of single day BID dosing every three weeks with consecutive dose escalations. The second part (Phase IB) consists of seven days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing patients could continue treatment within a compassionate use setting. Results and discussion. The present report describes our experience with the four patients with progressive squamous non-small cell lung cancer (NSCLC) that have received treatment with PPP. Despite more than seven months of PPP treatment as third or fourth line treatment, the reported patients did not develop any additional metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography (PET) scans of the patients demonstrated large central necrotic areas, which may suggest tumor response. At the same time, the study drug is so far well tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response has not been reported before in anti-IGF-1R treatment and will be subject to further studies in the present clinical trial.
|
|
| 4. |
|
|
| 5. |
- Mansoori, Sharmineh, et al.
(author)
-
A phase 2a clinical study on the safety and efficacy of individualized dosed mebendazole in patients with advanced gastrointestinal cancer
- 2021
-
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Mebendazole is used extensively for treatment of local gut helminthic and invasive echinococcus infections. Anticancer effects of mebendazole have been shown in experimental cancer models and in case studies in patients with advanced cancer. Given these observations, the aims of this study were to investigate safety and efficacy of individualized dosed mebendazole in the cancer indication. Patients with treatment refractory gastrointestinal cancer were treated with individualized dose adjusted mebendazole up to 4 g/day to target a serum concentration of 300 ng/ml. Efficacy and safety were assessed by CT-scans, clinical surveillance and blood sampling. Eleven patients were included in the study and 10 started the treatment phase. Two patients stopped treatment prior to and the remaining eight after tumour evaluation by CT-scan at 8 weeks, all due to progressive disease. Four patients also fulfilled criteria suggested for hyperprogression. Only five patients reached the target serum-mebendazole concentration. No severe adverse effects were observed. Individualized dose adjusted mebendazole is safe and well tolerated in patients with advanced cancer but all patients experienced rapid progressive disease. New approaches such as prodrug development and combination with other anticancer drugs seem needed for further exploration of mebendazole as an anticancer drug.
|
|
| 6. |
- Sevencan, Suat, 1983-, et al.
(author)
-
An Economical Comparison of Power-to-Gas Alternatives in Bozcaada - Turkey
-
Other publication (other academic/artistic)abstract
- Although currently conventional electricity generation methods dominate the market, the share of renewable energy systems is constantly increasing. Intermittent nature of solar and wind cause several problems. Power-to-gas is a method that can help with these problems by generating and storing hydrogen gas during off-peak hours so it can be reconverted into electricity via fuel cells and/or H2 internal combustion engines coupled with electricity generators during peak hours. In this study an economical evaluation of power-to-gas systems for an existing photovoltaic-Wind hybrid power system was made. Results indicate that although the photovoltaic-Wind may reduce the energy bill considerably when it is possible to sell electricity to the grid, coupling it with a power-to-gas system makes it unprofitable over the lifetime of the system.
|
|
| 7. |
- Sevencan, Suat, 1983-, et al.
(author)
-
Economic feasibility study of a fuel cell-based combined cooling, heating and power system for a data centre
- 2016
-
In: Energy and Buildings. - : Elsevier. - 0378-7788 .- 1872-6178. ; 111, s. 218-223
-
Journal article (peer-reviewed)abstract
- The energy use of data centres is increasing as the data storage needs increase. One of the largest items in the energy use of these facilities is cooling. A fuel cell-based combined cooling, heating and power system can efficiently meet such a centre's need for cooling and in the meantime generate enough electricity for the centre and more. In this paper the economic feasibility of a fuel cell-based combined cooling, heating and power system that meets the energy demands of such a facility is investigated using operational data from an existing data centre in Stockholm, Sweden. The results show that although the system is not feasible with current energy prices and technology it may be feasible in the future with the projected changes in energy prices.
|
|
| 8. |
- Sevencan, Suat, et al.
(author)
-
Fuel cell based cogeneration : Comparison of electricity production cost for Swedish conditions
- 2013
-
In: International journal of hydrogen energy. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0360-3199 .- 1879-3487. ; 38:10, s. 3858-3864
-
Journal article (peer-reviewed)abstract
- A good portion of greenhouse gas emissions is caused by the energy used in the built environment. Emission reduction goals may be achieved by combining cogeneration with fuel cells (PC). This paper investigates electricity production costs for PC based cogeneration systems with recent data for Swedish conditions. The types of FCs that are investigated are proton exchange membrane PC and molten carbonate FC. Based solely on cost, PC based cogeneration systems cannot compete with conventional systems. However, our results show that Molten Carbonate PC based cogeneration systems will be profitable by 2020. To compete with conventional systems, the capital cost, lifetime and efficiency of FCs must be improved. Creation of a reasonably broad market is essential since it will greatly help to reduce capital costs and operation and maintenance (O&M) costs, the dominating parts of the overall costs according to the analysis.
|
|
