Pharmacokinetics and Toxicity of Sodium Selenite in the Treatment of Patients with Carcinoma in a Phase I Clinical Trial: The SECAR Study.

BACKGROUND: Sodium selenite at high dose exerts antitumor effects and increases efficacy of cytostatic drugs in multiple preclinical malignancy models. We assessed the safety and efficacy of intravenous administered sodium selenite in cancer patients' refractory to cytostatic drugs in a phase I trial. Patients received first line of chemotherapy following selenite treatment to investigate altered sensitivity to these drugs and preliminary assessment of any clinical benefits. MATERIALS AND METHODS: Thirty-four patients with different therapy resistant tumors received iv sodium selenite daily for consecutive five days either for two weeks or four weeks. Each cohort consisted of at least three patients who received the same daily dose of selenite throughout the whole treatment. If 0/3 patients had dose-limiting toxicities (DLTs), the study proceeded to the next dose-level. If 2/3 had DLT, the dose was considered too high and if 1/3 had DLT, three more patients were included. Dose-escalation continued until the maximum tolerated dose (MTD) was reached. MTD was defined as the highest dose-level on which 0/3 or 1/6 patients experienced DLT. The primary endpoint was safety, dose-limiting toxic effects and the MTD of sodium selenite. The secondary endpoint was primary response evaluation. RESULTS AND CONCLUSION: MTD was defined as 10.2 mg/m(2), with a calculated median plasma half-life of 18.25 h. The maximum plasma concentration of selenium from a single dose of selenite increased in a nonlinear pattern. The most common adverse events were fatigue, nausea, and cramps in fingers and legs. DLTs were acute, of short duration and reversible. Biomarkers for organ functions indicated no major systemic toxicity. In conclusion, sodium selenite is safe and tolerable when administered up to 10.2 mg/m(2) under current protocol. Further development of the study is underway to determine if prolonged infusions might be a more effective treatment strategy.

Comparison of three different chest drainages after coronary artery bypass surgery--a randomised trial in 150 patients.

OBJECTIVE: Drainage of blood from the mediastinum and pleura following open cardiac procedures is usually carried out using one or more large-bore plastic chest tubes. Recently small diameter siliastic drains have been reported to evacuate blood with a better patient comfort. The efficacy and safety of different chest tubes have not yet been fully evaluated. METHODS: One hundred fifty patients undergoing coronary artery bypass surgery were randomised to have either Blake) 24F (Ethicon, Inc, Somerville, NJ), Argyle 32F plastic (Tyco Healthcare, Tullamore, UK) or Jostra 32F silastic (Maquet Cardiopulmonary AG, Hirrlingen, Germany) drains inserted for evacuation of postoperative bleeding. Bleeding rate per hour, total blood loss, patient discomfort during drain removal, residual pleural fluid at chest X-ray 3 days and 3 weeks after the operation were recorded. RESULTS: Bleeding pattern and total bleeding did not differ significantly in the three groups. Median blood loss was 615 ml (quartile range 390-820 ml) in the Blake-group, 750 ml (quartile range 430-870 ml) in the Jostra-group and 580 ml (quartile range 450-750 ml) in the Argyle-group, respectively (p=0.17). Pain at removal the day after the operation was similar in the three groups. Residual fluid in the left pleura did not differ significantly at 3 days (p=0.41) or at 3 weeks postoperatively (p=0.42). CONCLUSIONS: None of the three chest tubes was superior to drain postoperative bleeding or considering pain at removal. Local clinical routines and cost aspects should be the guide in choosing drainage system for open cardiac operations.

Pleurodesis in recurrent pleural effusions: a randomized comparison of a classical and a currently popular drug.

STUDY OBJECTIVES: Pleurodesis is generally regarded to give the best palliation in recurrent pleural effusion. Talc is now increasingly recommended but in our department quinacrine has been used successfully for many decades with good results and only minor side effects. It was therefore decided to make a prospective randomized clinical study comparing quinacrine (500 mg) with talc (5 g) with regard to efficacy and safety. METHODS: One hundred and ten eligible consecutive patients with recurrent and or malignant effusions, from 1 March 1996 till 31 March 1999 were randomized to chemical pleurodesis with either talc or quinacrine through a chest drainage tube after medical thoracoscopy. Patients were evaluated with chest radiographs at 2 weeks and 2, 4, and 6 months after pleurodesis. RESULTS: Chi-square test showed 84% power to distinguish between the groups and 10% to determine the primary endpoint. Primary success (fluid production < 50ml/24h within the first 6 days) was 96% of 56 patients with talc and 91% of 54 patients with quinacrine, a non-significant difference (P = 0.46). Quinacrine patients needed a repeated treatment in 31% (17 patients) and talc patients in 7% (4 patients) (P < 0.05). Side effects were minor with no significant difference between the substances. CONCLUSIONS: Both substances are effective. Talc treatment had less often to be repeated. This indicates that the recommendation of talc for pleurodesis is well founded. However, quinacrine is a good alternative.