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- Ekman, Simon, et al.
(författare)
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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
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:2, s. 140-148
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Probst, Johan, et al.
(författare)
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Thoracoscopic epicardial left atrial ablation in symptomatic patients with atrial fibrillation
- 2016
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 18:10, s. 1538-1544
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Tidskriftsartikel (refereegranskat)abstract
- The low efficacy rates reported for conventional catheter ablation of longstanding persistent atrial fibrillation (LPAF) have led to the development of alternative techniques such as minimal invasive surgical ablation, aiming for durable and contiguous transmural lesions. The aim was to evaluate the efficacy and safety of total thoracoscopic epicardial left atrial ablation (TELA-AF) procedures in a prospective study of severely symptomatic patients with either drug-resistant AF and/or failed attempts of catheter ablation. The TELA-AF surgical technique includes pulmonary vein isolation, left atrial (LA) 'box lesion', and partial vagal denervation. The LA appendage was excluded if deemed safe. Patients were followed with clinical evaluations and 12-lead electrocardiograms at 3, 6, and 12 months after the surgical intervention, complemented with a 7-day Holter monitoring after 6 and 12 months. Sixty patients, of whom 38 (63%) suffered from LPAF, underwent TELA-AF between November 2008 and December 2010. One patient with LPAF was lost to follow-up. At 12-month follow-up, 55/59 patients (93%) were free from atrial fibrillation (AF), while 7/59 patients (12%) suffered from recurrent LA tachycardia. Among patients with LPAF, 32/37 (86%) maintained sinus rhythm after 12 months. Adverse events included four perioperative bleedings requiring conversion to sternotomy in three cases, two ischaemic strokes and one transient ischaemic attack. The total thoracoscopic surgical ablation procedure is highly effective even in patients with LPAF, and it seems safe. The high rate of iatrogenic LA re-entrant tachycardia, however, warrants further improvement of the technique.
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