Final Results of a Phase I/II Trial of the Combination Bendamustine and Rituximab With Temsirolimus (BeRT) in Relapsed Mantle Cell Lymphoma and Follicular Lymphoma.

In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m2, day 1 + 2) and Rituximab (375 mg/m2, day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment. Overall, 39 (29 MCL, 10 FL) patients were included. Median age was 71 years and median pretreatment number was 2. Grade 3/4 non-hematologic adverse events were rare and included hyperglycemia in 3 patients (7%) and angioedema in 2 patients (5%). Infectious complications grade 3/4 were observed in 9 patients (23%). Hematologic grade 3/4 events included leukopenia in 22 (56%), neutropenia in 18 (46%), lymphopenia in 16 (41%) and thrombocytopenia in 14 patients (36%). An objective response (best response) was observed in 33/39 patients (89%; 24 MCL (89%) and 9 FL (90%)), including 14 CR (38%; 12 MCL (36%) and 2 FL (20%)). Median PFS is 1.5y for MCL and 1.82 years for FL, and median OS has not been reached for either entity. This data demonstrates promising efficacy of Temsirolimus in r/r MCL and FL with acceptable toxicity. The BeRT regimen may be used as a treatment option for both entities.

Effects of pentaerythritol tetranitrate on endothelial function in coronary artery disease: results of the PENTA study.

BACKGROUND: Pentaerythritol tetranitrate (PETN) differs from other organic nitrates by the lack of tolerance induction and by antioxidative properties. The purpose of this study was to determine the effect of PETN on endothelial function in patients with coronary artery disease (CAD). We hypothesized that the treatment with PETN improves endothelial function in patients with CAD. METHODS: In a prospective, double-blind study, we randomly assigned 80 patients to treatment for 8 weeks with oral PETN 80 mg t.i.d. (PETN) or placebo (C). The primary endpoint was the absolute change in brachial artery flow-mediated dilation (FMD) from baseline to follow-up. Furthermore, changes in nitroglycerin-mediated dilation (NMD), digital peripheral arterial tonometry (PAT) index, vascular shear stress, mean flow velocity, plasma bilirubin, C-reactive protein (CRP) and thiobarbituric acid reactive substances (TBARS), serum ferritin, and the activity of the PETN bioactivating enzyme aldehyde dehydrogenase-2 (ALDH-2) in peripheral blood mononuclear cells were analyzed. Raw data entry, data monitoring and statistical analysis were performed independently. RESULTS: The treatment groups were comparable regarding demographics, cardiovascular risk and concomitant medication. There was no difference in the change in FMD between the two treatment groups (mean +/- SD: PETN: +1.6 +/- 3.3% vs. C: +1.4 +/- 4.1%; P = 0.7). NMD increased after treatment with PETN and was higher compared with C (PETN: +3.8 +/- 5.5% vs. C: +0.6 +/- 4.2%; P = 0.004). Mean PAT index and ALDH-2 activity remained unchanged. Relative changes in mean flow volume (P = 0.04) and mean flow velocity (P = 0.01) upon ischemia increased in the PETN group versus C. Changes in bilirubin, ferritin, TBARS and CRP did not differ between the groups. CONCLUSIONS: We conclude that chronic PETN therapy in patients with CAD may be established for symptomatic treatment without adverse effects on endothelial function and with beneficial effects on the microcirculation.