| 1. |
- Kaye, S. B., et al.
(författare)
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Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval
- 2011
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 22:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L. P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy. Patients and methods: A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted. Results: Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357). Conclusion: The superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.
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| 2. |
- Poveda, A., et al.
(författare)
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Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer : outcomes in the partially platinum-sensitive (platinum-free interval 6-12 months) subpopulation of OVA-301 phase III randomized trial
- 2011
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 22:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD) over PLD alone in relapsed ovarian cancer. The optimal management of patients with partially platinum-sensitive relapse [6-12 months platinum-free interval (PFI)] is unclear. Patients and methods: Within OVA-301, we therefore now report on the outcomes for the 214 cases in this subgroup. Results: Trabectedin/PLD resulted in a 35% risk reduction of disease progression (DP) or death [hazard ratio (HR) = 0.65, 95% confidence interval (CI), 0.45-0.92; P = 0.0152; median progression-free survival (PFS) 7.4 versus 5.5 months], and a significant 41% decrease in the risk of death (HR = 0.59; 95% CI, 0.43-0.82; P = 0.0015; median survival 23.0 versus 17.1 months). The safety of trabectedin/PLD in this subset mimicked that of the overall population. Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), although patients in the trabectedin/PLD arm had a slightly lower proportion of further platinum (49% versus 55%). Importantly, patients in the trabectedin/PLD arm survived significantly longer after subsequent platinum (HR = 0.63; P = 0.0357; median 13.3 versus 9.8 months). Conclusion: This hypothesis-generating analysis demonstrates that superior benefits with trabectedin/PLD in terms of PFS and survival in the overall population appear particularly enhanced in patients with partially sensitive disease (PFI 6-12 months).
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| 3. |
- Wong, Wilson, et al.
(författare)
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Lineage-Committed Pancreatic Progenitors and Stem Cells
- 2014
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Ingår i: ADULT STEM CELLS, 2ND EDITION. - TOTOWA : HUMANA PRESS INC. - 9781461495697 ; , s. 339-357
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Bokkapitel (refereegranskat)abstract
- Type 1 diabetes is an autoimmune disease where self-reactive T cells attack and destroy insulin-producing beta cells. The prevalence of type 1 diabetes is increasing worldwide, but therapeutic options to cure diabetes are presently restricted to transplantation of cadaveric insulin-producing (islet) cells. One of the limitations to success of islet transplantation therapy is the lack of donor pancreatic islets. An alternative is to generate insulin-producing (beta-like) cells in the laboratory. Various sources of stem/progenitor cells, such as those from the umbilical cord blood, bone marrow, as well as embryonic stem (ES) cells/induced pluripotent stem (iPS) cells, have been tested for their potential to differentiate into an endocrine pancreatic lineage. These studies have confirmed that it is very difficult to generate a cell type that is able to produce physiologically significant amounts of insulin and secrete it in response to glucose, in a manner similar to that demonstrated by pancreatic beta cells. This chapter reviews the differentiation and commitment of adult pancreatic progenitor/stem cells to endocrine pancreatic lineage and discusses the practical difficulties towards using these for treatment of diabetes in humans.
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