RESUMEN
BACKGROUND: The phase I trial of the humanized anti-CD26 monoclonal antibody YS110 for CD26-expressing tumors was conducted recently. The present study identifies a potential prognostic biomarker for CD26-targeted therapy based on the phase I data. METHODS: Box and Whisker plot analysis, Scatter plot analysis, Peason product moment correlation/Spearman's rank-difference correlation, Bar graph analysis, and Receiver Operating Characteristics (ROC) were used to examine the correlation between sCD26 titer variation with YS110 administration and tumor volume change, RECIST criteria evaluation and progression free survival (PFS). Mechanism for serum sCD26 titer variation was confirmed by in vitro experimentation. RESULTS: Serum sCD26/DPP4 titer was reduced following YS110 administration and gradually recovered until the next infusion. Serum sCD26/DPP4 titer before the next infusion was sustained at lower levels in Stable Disease (SD) cases compared to Progressive Disease cases. ROC analysis defined the cut-off level of serum sCD26/DPP4 titer variation at day 29 pre/post for the clinical outcome of SD as tumor response or PFS. In vitro experimentation confirmed that YS110 addition reduced sCD26 production from CD26-expressing tumor and non-tumor cells. CONCLUSIONS: Our study indicates that serum sCD26/DPP4 titer variation in the early phase of YS110 treatment is a predictive biomarker for evaluating therapeutic efficacy.
RESUMEN
PURPOSE: To compare the ocular hypotensive effect of travoprost plus timolol (TTFC) and latanoprost plus timolol fixed combinations (LTFC) in patients with normal-tension glaucoma (NTG). METHODS: A two-sequence 12-week, multicenter, prospective, randomized, single-blinded, crossover clinical trial examined 59 NTG patients. If both eyes were eligible, only one eye (chosen at random) was used for analytical purposes. After a 12-week run-in period with dorzolamide plus timolol fixed combination (DTFC), patients were randomized into one of the two crossover sequences of treatment for 12 weeks with TTFC or LTFC and were subsequently crossed over to the alternative treatment for a further 12 weeks. The primary endpoint was reduction in IOP after 12 weeks of each treatment sequence. The effect of treatment on IOP was assessed using a linear mixed model. RESULTS: The mean baseline IOP was 14.8 ± 3.3 mm Hg (95% confidence interval [CI], 14.1-15.3 mm Hg) for treatment with DTFC. The TTFC treatment period showed consistently lower mean IOP compared with LTFC treatment period at all measurement time points. Mean reduction in IOP at 12 weeks was significantly greater in the TTFC group than in the LTFC group (-2.4 ± 2.3 mm Hg vs. -1.1 ± 2.3 mm Hg; P = 0.021). No interaction between the drug and treatment sequence was detected. The effects of intraocular lens implantation and measurement time were also not significant. The tolerability profiles of both treatments were similar. CONCLUSIONS: The additional reduction in IOP was greater with TTFC than with LTFC, and their tolerability profiles were similar. (http://www.umin.ac.jp/ctr/ number, UMIN 000005974.).