Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial.

BACKGROUND: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. RESULTS: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. CONCLUSION: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.

In vitro hemolysis by mechanical heart valve prostheses with tilting disc.

Hemolytic and subhemolytic blood damage by mechanical heart valve prostheses have been observed in both clinical and in vitro investigations. A direct comparison between these studies is not possible. Nevertheless the transfer of some in vitro results to the behaviour of the valve in situ may be performed considering the similarity principle. This requires the use of dimensionless similarity numbers such as the plasma's hemoglobin concentration (PHb) or others, instead of dimensioned parameters. To evaluate the in vitro hemolysis of valve prosthesis a test chamber filled with human banked blood was used. An artificial ventricle ensuring an oscillatory flow through the valve was also used. The rise of PHb was evaluated in terms of a similarity number, called the lysis number. This number describes the probability of destroying a single red blood cell participating once in the hemolytic process under consideration. The lysis number, a Björk-Shiley valve (TAD 29), was found to be in the order of 2 x 10(-4). From this, the survival time of erythrocytes in patients with an artificial heart valve was estimated. It was found to be in the order of 20 d of T50 Cr in agreement with clinical results.