000			nab a22 7a 4500
999			_c17025 _d17025
003			PC17025
005			20221018121132.0
008			221018b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_9433 _aSepúlveda Sánchez, Juan Manuel _eOncología Médica
245	0	0	_aFirst-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. _h[artículo]
260			_bClinical cancer research : an official journal of the American Association for Cancer Research, _c2015
300			_a21(3):553-60.
500			_aFormato Vancouver: Rodon J, Carducci MA, Sepulveda Sánchez JM, Azaro A, Calvo E, Seoane J et al. First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma. Clin Cancer Res. 2015 Feb 1;21(3):553-60.
501			_aPMID: 25424852 PMC4337847
504			_aContiene 34 referencias
520			_aPurpose: TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer. Experimental design: Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria. Results: In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥ 6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥ 6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events. Conclusions: On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation.
710			_9303 _aServicio de Oncología Médica
856			_uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337847/ _yAcceso libre
942			_2ddc _cART _n0